From birth to death, every cell uses intracellular Ca²⁺ to regulate its activities.
How can so simple an ion be used to control so much?

Research Interests

Calcium: a ubiquitous intracellular messenger

Ca2+ channels in the plasma membrane and the ER generate local increase in cytosolic Ca2+ concentration

Every cell actively extrudes Ca²⁺ from its cytosol and thereby generates steep Ca²⁺ concentration gradients across both the plasma membrane that surrounds it and across the membranes that surround certain intracellular organelles, notably the  endoplasmic reticulum. Many different extracellular signals precisely control the opening of Ca²⁺ channels within these membranes, allowing a rapid flow of Ca²⁺ into  the cytosol. The ensuing increase in cytosolic Ca²⁺ concentration controls almost  every  aspect of cellular activity, from fertilization to programmed cell death, and  from  release of neurotransmitters at synapses to control of muscle contraction. But,  excessive or prolonged increases in cytosolic Ca²⁺ concentration are toxic. To use Ca²⁺as an intracellular signal is to befriend a potentially lethal foe: cytosolic Ca²⁺signals must be precisely controlled.

Because Ca²⁺ diffuses slowly in cytosol, the Ca²⁺ concentration close to the mouth of an open Ca²⁺ channel may be very much higher then in the rest of the cell. Such local Ca²⁺ signals add enormously to the versatility of Ca²⁺ signals by allowing the Ca²⁺ passing through one channel to regulate different processes to the Ca²⁺ passing through a different Ca²⁺ channel. What determines the specific associations between Ca²⁺ channels and Ca²⁺ sensing proteins?

Most Ca²⁺ channels and Ca²⁺ transporters are subject to feedback regulation by cytosolic Ca²⁺, and Ca²⁺ signals are often delivered to the cytosol as transient Ca²⁺ spikes. Our work aims to understand, ultimately at the structural level, how these Ca²⁺ channels are regulated and how Ca²⁺ signals are decoded by cells.

The structure of IP3 Many G-protein coupled receptors and other receptors too, stimulate phospholipase C, which hydrolyses PIP2 to produce the two intracellular messengers, IP3 and diacylglycerol (DAG).

IP₃ receptors - understanding the workings of an intracellular Ca²⁺ channel

Inositol 1,4,5-trisphosphate (IP₃) receptors are intracellular Ca²⁺ channels; they are expressed in most eukaryotic cells and they are largely responsible for mediating the release of Ca²⁺ from intracellular stores evoked by many cell-surface receptors.

Functional IP₃ receptors are homo- or hetero-tetrameric assemblies of subunits encoded by three related mammalian genes and their splice variants. Each of these assemblies forms a Ca²⁺ channel regulated by IP₃ and cytosolic Ca²⁺, but the subtypes differ in their distributions and in some aspects of their regulation.

What are the functions of the different IP₃ receptor subtypes and why are they so precisely assembled into heterotetrameric assemblies? What controls the expression of IP₃ receptors? How do IP₃ and Ca²⁺ interact to control whether the Ca²⁺ channel of the IP₃ receptor will open? How is IP₃ recognised by IP₃ receptors, and how does that recognition lead to channel opening? Where does Ca²⁺ bind?

Recombinant IP₃ receptors

Sf9 cells: The blue marker indicates over-expression of the IP3 receptor in the cells infected with baculovirus. Spodoptera frugiperda: the insect from which the Sf9 cell line was first established. Rapid Screening of the effects of novel ligands on Ca2+ release from recombinant IP3 receptors.

Most cells express IP₃ receptors and many express several subtypes. To address the roles of specific IP₃ receptors and the structural basis of their function, we need systems in which we can express only specific IP₃ receptor subtypes, mutated forms of the receptors, and fragments of them. Kurosaki and his colleagues established a DT40 cell line devoid of all IP₃ receptors and this now provides a null-background for expression of IP₃ receptors. We use these cells, transfected to express appropriate IP₃ receptors, in a variety of functional assays, including single channel recording using patch-clamp and high-throughput assays using luminal Ca²⁺ indicators. We use baculovirus to allow massive over-expression of each IP₃ receptor subtype in insect Sf9 cells to address the recognition properties of the receptors and for structural studies. Bacteria allow expression of large amounts of fragments of IP₃ receptors to examine more closely the structural basis of ligand recognition and the conformational changes that follow IP₃ binding.

Novel ligands of IP₃ receptors

Structures of some agonists of IP3 receptors

In a longstanding collaboration with Barry Potter and his colleagues at Bath, we are interested in defining the structural basis of ligand recognition by IP₃ receptors: which features of the ligands and binding site contribute to high-affinity binding and which are important for activation of the receptor?

Adenophostin A, first isolated from the fungus Penicillium brevicompactum, is the most potent known agonist of IP₃ receptors and it is not metabolized by the enzymes that degrade IP₃. Adenophostin A and many related structures have now been synthesised and their biological activity assessed to provide a comprehensive description of the determinants of their high-affinity binding.

Analogues of IP₃ modified at the 2-OH position are also proving useful in defining the structural determinants of agonist and antagonist binding. Dimers of IP₃, linked via their 2-OH groups, provide the highest affinity analogues of IP₃ known, but they are partial agonists and they and IP₃ interact differently with the N-terminal of IP₃ receptors. What can this tell us about the way in which IP₃ activates IP₃ receptors?

Additional 2-modified analogues of IP₃ allow the space around the IP₃-binding site within the 3D structure of the tetameric IP₃ receptor to be mapped and they provide routes to fluorescent and photoreactive analogues of IP₃.

Recording opening and closing of single IP3 receptors. By forming a very tight seal between the tiny tip of a glass microelectrode and the membrane, the miniscule currents flowing through single IP3 receptors can be detected and amplified. The trace shows two IP3 receptors caught beneath a recording pipette stimulated with IP3, as they flit between open and closed states.

Watching IP₃ receptors at work

The patch-clamp technique, developed by Neher and Sakmann, allows the opening and closing of single channels to be recorded with very high temporal resolution. Until quite recently, such methods were the only means of observing the workings of single channels in their native membranes: they have transformed our understanding of how channels open and close, and select between different ions.

Advanced optical methods have extended these opportunities: it is now possible to attempt to measure IP₃ binding to single IP₃ receptors and to then follow the conformational change through each IP₃ receptor.

Our recent work with patch-clamp recording from recombinant IP₃ receptors in the nuclear envelope or plasma membrane has established that B lymphocytes express just 2-3 IP₃ receptors in the plasma membrane and it has begun to define the initial conformational changes that follow IP₃ binding.

Structure of IP₃ receptors

Reconstruction of 3D structure of IP3 receptor with gold-IP3 bound using single particle analysis of EM images

IP₃ receptors are huge proteins: four subunits each comprising about 2700 amino acid residues. In collaboration with the group of Ed Morris at The Institute of Cancer Research, we are using reconstructing a 3D structure of the IP₃ receptor purified from a native source using single particle analysis of images collected by electron microscopy. The work so far has provided a structure of the IP₃ receptor with and without IP₃ bound, and using a form of IP₃ with a gold particle attached we have established the location of the IP₃-binding sites within the 3D structure. Future work using recombinant IP₃ receptors with appropriately located tags should identify the location of other key parts of the primary sequence within the 3D structure. As more high-resolution structures of fragments of the IP₃ receptor become available, these can then be docked into the 3D structure. Ultimately such analyses seek to provide a structural view of how IP₃ regulates its receptor.

Regulation of IP3 receptors by Ca2+ Thapsia gargantua, source of thapsgargin, an irreversible inhibitor of the ER Ca2+ pump

Calcium and IP₃ receptors - a complex relationship

All three mammalian IP₃ receptor subtypes are regulated by IP₃ and Ca²⁺. Under the conditions used for most experiments - pre-incubation of permeabilized cells in cytosol-like media containing different [Ca²⁺] - modest increases in [Ca²⁺] potentiate responses to IP₃, while further increases are inhibitory. Our previous work combining radioligand binding with functional assays of ⁴⁵Ca²⁺ release established that two different Ca²⁺ binding sites, which differed in their relative abilities to bind Ca²⁺ and Sr²⁺, mediated the stimulatory and inhibitory effects of Ca²⁺.

To address this interplay between Ca²⁺ and IP₃ with greater temporal resolution, we built a superfusion apparatus that allows IP₃-evoked ⁴⁵Ca²⁺ release from permeabilized cells to be measured with up to 9ms temporal resolution. Our results from hepatocytes (which express largely type 2 IP₃ receptors) suggest that IP₃ binding controls what Ca²⁺ does to the IP₃ receptor. With no IP₃ bound, only an inhibitory Ca²⁺-binding site is accessible, whereas after IP₃ binding the inhibitory site is occluded and a stimulatory Ca²⁺-binding site is exposed. Ca²⁺ released by an active IP₃ receptor can therefore inhibit its unliganded neighbours ("lateral inhibition"), but not itself. This mechanism may be important for the controlled recruitment of elementary Ca²⁺ release events. The first IP₃ receptor within a cluster to open providing the Ca²⁺ needed to cause rapid opening of neighbouring receptors that have IP₃ bound, while simultaneously inhibiting those that have no IP₃ bound

cAMP synapses: another way to regulate Ca²⁺ mobilization

In HEK cells expressing human PTH receptors, carbachol (CCh), via IP3,stimulates release of Ca2+ stores; PTH alone is ineffective, but it massively potentiates the response to CCh

There are many interactions between Ca²⁺ and cAMP, the best known and most commonly used intracellular messengers. We have established that receptors that stimulate cAMP formation also potentiate IP₃-evoked Ca²⁺ release by a mechanism that involves neither protein kinase A nor EPACs, the usual targets of cAMP. Instead very high concentrations of cAMP generated within intracellular "cAMP synapses" close to receptors directly sensitize IP₃ receptors to IP₃. This form of communication between receptors, cAMP and IP₃ receptors is digitally coded, that is each synapse operates as on-off switch, with more switches thrown as the intensity of the extracellular stimulus is increased. Other responses to cAMP may be coded as analogue signals, with the response smoothly graded as the global cAMP concentration increases within the cell.

Confocal microscopy to examine targeting of IP3 receptors in COS cells

Putting IP₃ receptors in their place

One of the more striking features of intracellular Ca²⁺ signals is their precise spatial organisation: Ca²⁺ increases occur in specific parts of the cell and thereby regulate only a subset of the many processes that can be regulated by Ca²⁺. What are the signals that keep IP₃ receptors in the endoplasmic reticulum and even within specific parts of the ER? What allows IP₃ receptors to be expressed in other organelles and even at the plasma membrane of some cells? We are tackling these questions using IP₃ receptors and fragments of them tagged with variants of green fluorescent protein to allow their subcellular distribution to be followed using confocal microscopy.

Ca²⁺ entry - another source of Ca²⁺ signals

Quantitative PCR and western blotting to measure expression of TRP proteins in A7r5 cells Ca2+ entry in A7r5 cells.

Receptors that stimulate IP₃ invariably stimulate both release of Ca²⁺ from intracellular stores (mediated by IP₃ receptors) and Ca²⁺ entry across the plasma membrane. How the latter is regulated remains a major concern of many labs. In most cells, depletion of intracellular Ca²⁺ stores activates a Ca²⁺-permeable channel in the plasma membrane, the so-called "capacitative" or "store-regulated" Ca²⁺ entry pathway. Recent work has established the role of Orai in contributing to formation of the store-operated Ca²⁺ channel and of STIM in mediating its regulation by empty Ca²⁺ stores, but the physiological significance of this Ca²⁺ entry pathway is uncertain. Using A7r5 vascular smooth muscle cells, we have shown that two distinct Ca²⁺ entry pathways are reciprocally regulated by vasopressin, and that arachidonic acid and NO are important elements of the sequence linking the receptor to these Ca²⁺ entry pathways. When vasopressin is present, all Ca²⁺ entry is mediated by a non-capacitative (NCCE) pathway, and this is followed by a rapid transient activation of the capacitative (CCE) pathway when vasopressin is removed. We speculate that Ca²⁺ entering via each of these pathways may be selectively directed to different intracellular targets. This may allow vasopressin to first activate the cell (using Ca²⁺ from the NCCE pathway) and then actively promote recovery (using Ca²⁺ entering via the CCE pathway), when vasopressin dissociates from its receptor.

In the same cells in which vasopressin reciprocally regulates CCE and NCCE, 5-HT which also activates phospholipase C, activates only CCE. Hence 2 receptors sharing many elements of a signalling pathway nevertheless evoke very different patterns of Ca²⁺ entry. What are the mechanisms that allow such receptor-specific regulation of distinct Ca²⁺ entry pathways and what is its functional significance?

Although IP₃ receptors are best known as intracellular Ca²⁺ channels, we have also shown that a very small number of IP₃ receptors are expressed in the plasma membrane of DT40 cells where they are responsible for about half the Ca²⁺ entry evoked by the B cell receptor. The remaining Ca²⁺ entry is via CCE. How can a cell reliably direct so few channels to the plasma membrane? What are the functional effects of Ca²⁺ entry via CCE and IP₃ receptors?

Decoding: making the most of Ca²⁺ signals

Decoding Ca²⁺ entry signals in A7r5 cells.

Long-lasting inhibition of type 3 adenylyl cyclase selectively mediated by IP3-evoked ca2+release and activation of CaMKII

A7r5 cells, originally isolated from vascular smooth muscle, express several different receptor-regulated Ca²⁺ entry pathways and we have the tools to selectively stimulate or inhibit each of them. What roles do they different pathways fullfil? Are different cellular responses selectively coupled to increases in cytosolic [Ca²⁺] evoked by different Ca²⁺ entry pathways.

Rather unexpectedly, inhibition of adenylyl cyclase by vasopressin in A7r5 cells is long-lasting and mediated selectively by IP₃-evoked release of Ca²⁺ from intracellular stores. What are the mechanisms that selectively couple regulation of adenylyl cyclase to IP₃-evoked Ca²⁺ release and how does so brief a Ca²⁺ signal cause such long-lasting inhibition?

Ca²⁺ and contraction in human uterus.

The mechanisms controlling human labour are not well understood. Induction of labour with drugs (prostaglandins) is often ineffective leading to high rates of caesarean section; and because there is no effective treatment for delaying premature labour, prematurity remains the major cause of newborn mortality and disability. In collaboration with Steve Thornton at Warwick, we are using strips of human myometrium (taken during Caesarean sections) to define the mechanisms linking Ca²⁺ to contraction in human uterus and the means whereby the hormone oxytocin modulates contractility.

Joining the Lab

The lab is very well equipped to provide a variety of complementary approaches to understanding the structural basis of IP₃ receptor function and the decoding of Ca²⁺ signals. Facilities include:

• Patch-clamp rigs
• Single cell and confocal imaging
• Rapid kinetics analysis of IP₃ recceptor function
• Quantitative PCR and blotting equipment
• High-throughput analysis of Ca²⁺ signals
• Fluorescence polarization
• Molecular biology and large scale production of proteins for structural studies

Summer students often join the lab for 8-10 weeks during the long vacation to undertake a research project. The best time to enquire about such opportunities is in January.

Graduate Students (Ph.D or M.Phil.) are admitted via the Department. Details of application procedures are found at: http://www.phar.cam.ac.uk/phd/index.html
Please feel free to contact Prof. Colin Taylor at any time with informal enquiries about joining the lab before submitting a full application.

Postdoctoral positions are advertised on www.jobs.ac.uk when they arise, but informal enquiries can be considered at any time.

Visitors are welcome to join the lab whenever space and funding allow.

All Publications: Details of the most recent/up-to-date publications can be found at: www.phar.cam.ac.uk/docs/taylor publications.htm

Publications

2006

• Mochizuki, T, Kondo, Y, Abe, H, Taylor, CW, Potter, BVL, Matsuda, A & Shuto, S (2006) Design and synthesis of 5'-deoxy-5'phenyladenophostin A, a highly potent IP₃ receptor ligand. Org. Lett. 8, 1455-1458.
• Terauchi, M, Abe, H, Tovey, SC, Dedos, SG, Taylor, CW, Paul, M, Trusselle, M, Potter, BVL, Matsuda, A & Shuto, S (2006) A systematic study of C-glucoside trisphosphates as myo-inositol trisphosphate receptor ligands. Synthesis of β-C-glucoside trisphosphates based on the conformational restriction strategy. J. Med. Chem. 49, 1900-1909.
• Suresham, KM, Trusselle, M, Tovey, SC, Taylor, CW & Potter, BVL (2006) Guanophostin: synthesis and evaluation of a high affinity agonist of the inositol trisphosphate receptor. Chem. Comm. 19, 2015-2017. Front cover.
• Woodcock, NA, Taylor, CW & Thornton, S (2006) Prostaglandin F2α increases the sensitivity of the contractile apparatus to Ca²⁺ in human myometrium. Am. J. Obs. Gyn. In press.
• Dellis, O, Dedos, SG, Tovey, SC, Rahman, U-T, Dubel, SJ & Taylor, CW (2006) Ca²⁺ entry through plasma membrane IP₃ receptors. Science, 313, 229-233. Commentary in Science 313, 183-184.
• Tovey, SC, Sun, Y & Taylor, CW (2006) Rapid functional assays of intracellular Ca²⁺ channels. Nature Protocols 1, 258-262.
• Mochizuki, T, Kondo, Y, Abe, H, Tovey, SC, Dedos, SD, Taylor, CW, Paul, M, Potter, BVL, Matsuda, A & Shuto, S (2006) Synthesis of adenophostin A analogues conjugating an aromatic group at the 5'-position as potent IP₃ receptor ligands. J. Med. Chem. 49, 5750-5758.
• Liu, Y & Taylor, CW (2006) Stimulation of arachidonic acid release by vasopressin in A7r5 vascular smooth muscle cells mediated by Ca²⁺-stimulated phospholipase A2. FEBS Lett. 580, 4114-4120.
• Dedos, SG, Tovey, SC & Taylor, CW (2006) Signalling from parathyroid hormone. Biochem. Soc. Trans. 34, 515-517.
• Taylor, CW (2006) Store-operated Ca²⁺ entry: a STIMulating stOrai. Trends Biochem. Sci. In press.
• Taylor, CW & Dellis, O (2006) Plasma membrane IP₃ receptors. Biochem. Soc. Trans. In press.

2005

• Terauchi, M, Yahiro,Y, Abe, H, Ichikawa, S., Tovey, SC, Dedos, SG, Taylor, CW, Potter, BVL, Matsuda, A & Shuto, S. (2005) Synthesis of 4,8-anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate as a novel IP₃ receptor ligand using a stereoselective radical cyclization reaction based on a conformational restriction strategy. Tetrahedron. 61, 3697-3707.
• Laude, AJ, Tovey, SC, Dedos, SG, Potter, BVL, Lummis, SCR & Taylor, CW (2005) Rapid functional assays of recombinant IP₃ receptors. Cell Calcium 38, 45-51.
• Borissow, CN, Black, SJ, Paul, M, Tovey, SC, Dedos, SG, Taylor, CW & Potter, BVL (2005) Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity. Org. Biomol. Chem. 3, 245-252.
• Dyer, JL, Liu, Y, Pino de la Huerga, I & Taylor, CW (2005) Long-lasting inhibition of adenylyl cyclase selectively mediated by inositol 1,4,5-trisphosphate-evoked calcium release. J. Biol. Chem. 280, 8035-8044.
• Moneer, Z, Pino de la Huega, I, Taylor, EC, Broad, LM, Liu, Y, Tovey, SC, Staali, L & Taylor, CW (2005) Different phospholipase C-coupled receptors differentially regulate capacitative and non-capacitative Ca²⁺ entry in A7r5 cells. Biochem. J. 389, 821-829.
• Taylor, CW & Tovey, SC (2005) What's in store for Ca²⁺ oscillations? J. Physiol. 562, 645.

2004

• Woodcock, N, Taylor, CW & Thornton, S (2004) Effect of an oxytocin receptor antagonist and rho kinase inhibitor on the [Ca²⁺]_i sensitivity of human myometrium. Am. J. Obs. Gynecol. 190, 222-228.
• Riley, AM, Laude, AJ, Taylor, CW & Potter, BVL. (2004) Dimers of D-myo-inositol 1,4,5-trisphosphate: design, synthesis, and interaction with Ins(1,4,5)P₃ receptors. Bioconj. Chem. 15, 278-289.
• Parker, AKT, Gergely, F & Taylor CW (2004) Targeting of inositol 1,4,5-trisphosphate receptors to the endoplasmic reticulum by multiple signals within their transmembrane domains. J. Biol. Chem. 279, 23797-23805.
• Taylor, CW, da Fonseca, PCA & Morris EP (2004) IP₃ receptors: the search for structure. Trends Biochem. Sci. 29, 210-219.
• Taylor, CW, Morris, E & da Fonseca, P (2004) IP₃ receptors. In Encyclopedia of Biological Chemistry Vol. 2 (Ed. W Lennarz & M D Lane), pp478-481.
• Taylor, CW & Moneer, Z (2004) Regulation of capacitative and non-capacitative Ca²⁺ entry in A7r5 vascular smooth muscle cells. Biol. Rev. 37, 6411-645.
• Rossi, AM & Taylor, CW (2004) Ca²⁺ regulation of inositol 1,4,5-trisphosphate receptors: can Ca²⁺ function without calmodulin? Mol. Pharmacol. 66, 199-203.

2003

• Tovey, SC, Goraya, TA & Taylor, CW (2003) Parathyroid hormone increases the sensitivity of inositol trisphosphate receptors by a mechanism that is independent of cyclic AMP. Br. J. Pharmacol. 138, 81-90.
• Moneer, Z, Dyer, JA & Taylor, CW (2003) Nitric oxide mediates reciprocal regulation of capacitative and non-capacitative Ca²⁺ entry by vasopressin. Biochem. J. 370, 439-448.
• Turvey, MR, Laude, AJ, Ives, OH, Seager, WH, Taylor, CW & Thorn, P (2003) Modulation of IP₃-sensitive Ca²⁺ release by 2,3-butanedione monoxime. Pflüg. Archiv. 445, 614-621.
• daFonseca, PCA, Morris, SA, Nerou, EP, Taylor, CW & Morris, EP (2003) Domain organisation of the type 1 inositol 1,4,5-trisphosphate receptor as revealed by single particle analysis. Proc. Natl. Acad. USA. 100, 2936-3941.
• Wagner, GK, Riley, AM, Rosenberg, HJ, Taylor, CW, Guse, AH and Potter, BVL (2003) Analogues of cyclic adenosine 5'-diphosphate ribose and adenophostin A, nucleotides in cellular signal transduction. Nucl. Acid. Res. Suppl. 3, 1-2.
• Rosenberg, HJ, Riley, AM, Laude, AJ, Taylor, CW & Potter BVL (2003) Synthesis and Ca²⁺-mobilizing activity of purine-modified mimics of adenophostin A: a model for adenophostin A-Ins(1,4,5)P3 receptor interaction. J. Med. Chem. 46, 4860-4871.
• Taylor, CW & Laude, AJ (2003) IP₃ receptors and their regulation by calmodulin and Ca²⁺. Cell Calcium.35, 3 21-334.
• Taylor, CW (2003) IP₃ receptors. In Handbook of Cellular Signalling. Volume 2 (Eds. R Bradshaw & E Dennis), Elsevier Science (USA) pp41-43.
• Taylor, CW & Swatton, JE (2003) Regulation of IP₃ receptors by IP₃ and Ca²⁺. In Understanding Calcium Dynamics. Experiments and Theory (Eds. M Falke & D Malchow), Springer-Verlag, Berlin, pp1-15.

2002

• Wissing, F, Nerou, EP & Taylor, CW (2002) A novel Ca²⁺-induced Ca²⁺ release mechanism mediated by neither inositol trisphosphate nor ryanodine receptors. Biochem. J. 361, 605-611.
• Moneer, Z & Taylor, CW (2002) Reciprocal regulation of capacitative and non-capacitative Ca²⁺ entry in A7r5 vascular smooth muscle cells: only the latter operates during receptor activation. Biochem. J. 362, 12-21
• Kidd, JF, Pilkington, MF, Schell, MJ, Fogarty, KE, Skepper, JN, Taylor, CW & Thorn, P (2002) Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J. Biol. Chem. 277, 6504-6510.
• Swatton, JE & Taylor, CW (2002) Fast biphasic regulation of type 3 inositol trisphosphate receptors by cytosolic calcium. J. Biol. Chem. 277, 17571-17579.
• Riley, AM, Morris, SA, Nerou, P, Correa, V, Potter, BVL & Taylor, CW (2002) Interactions of inositol 1,4,5-trisphosphate receptors with synthetic poly(ethylene glycol)-linked dimers of IP₃ suggest close spacing of the IP₃-binding sites. J. Biol. Chem. 277, 40290-40295.
• Morris, SA, Nerou, EP, Riley, AM, Potter, BVL & Taylor, CW (2002) Determinants of adenophostin A binding to inositol trisphosphate receptors. Biochem. J. 367, 113-120.Taylor CW (2002) Inositol trisphosphate (IP₃) receptors. In Encyclopedia of Molecular Medicine (Ed. TE Creighton), John Wiley and Sons, New York. pp1758-1761.
• Taylor, CW (2002) Regulation of Ca²⁺ entry pathways by both limbs of the phosphoinositide pathway. (2002) In, Role of the Sarcoplasmic Reticulum in Smooth Muscle. Novartis Foundation Symposium 246, John Wiley and Sons, Chichester. pp91-107.
• Taylor, CW (2002) Controlling calcium entry. Cell 111, 767-769.

2001

• Wang, Y, Chen, J, Wang, Y, Taylor, CW, Hirata, Y, Hagiwara, H, Mikoshiba, K, Toyo-oka, T, Omata, M & Sakaki, Y (2001) Crucial role of type 1, but not type 3, inositol 1,4,5-trisphosphate (IP₃) receptors in IP₃-induced Ca²⁺ release, capacitative Ca²⁺ entry, and proliferation of A7r5 vascular smooth muscle cells. Circ. Res. 88, 202-209.
• Nerou, EP, Riley, AM, Potter, BVL & Taylor, CW (2001) Selective recognition of inositol phosphates by subtypes of inositol trisphosphate receptor. Biochem. J. 355, 59-69.
• Correa, V, Riley, AM, Shuto, S, Horne, G, Nerou, P, Marwood, RD, Potter, BVL & Taylor, CW (2001) Structural determinants of adenophostin A activity at inositol trisphosphate receptors. Mol. Pharmacol. 59, 1206-1215.
• Riley, AM, Correa, V, Mahon, MF, Taylor, CW & Potter, BVL (2001) Bicyclic analogs of D-myo-inositol 1,4,5-trisphosphate related to adenophostin A: synthesis and biological activity. J. Med. Chem. 44, 2108-2117.
• Rosenberg, HJ, Riley, AM, Marwood, R, Correa, V, Taylor, CW & Potter, BVL (2001) Xylopyranoside-based mimics of D-myo-inositol-trisphosphate: synthesis and effect of stereochemistry on biological activity. Carbohydr. Res. 332, 53-66.
• Swatton, JE, Morris, SA & Taylor, CW (2001) Functional properties of Drosophila IP₃ receptors. Biochem. J. 359, 435-441.Taylor, CW (2001) Calcium. In The Oxford Companion to the Body (Ed. C Blakemore) Oxford University Press. pp123-124.
• Taylor, CW (2001) Cell Signalling. In The Oxford Companion to the Body (Ed. C Blakemore) Oxford University Press. pp135-136.
• Taylor, CW (2001) InsP3/ryanodine receptors In The Sigma-RBI Handbook of Receptor Classification and Signal Trqnsduction, Fourth Edition. (Ed. K Watling). pp 166-167.
• Taylor, CW & Thorn, P (2001) Calcium signalling: IP₃ rises again.and again. Curr. Biol. 11, R352-R355.

2000

• Marwood, RD, Correa, V, Taylor, CW & Potter, BVL (2000) Synthesis of adenophostin A. Tetrahedron Asymetry. 11, 397-403.
• Short, AD & Taylor, CW (2000) Parathyroid hormone controls the size of the intracellular Ca²⁺ stores available to receptors linked to inositol trisphosphate formation. J. Biol. Chem. 275, 1807-1813.
• Adkins, CE, Morris, SA, De Smedt, H, Sienaert, I, Torok, K, & Taylor, CW (2000) Ca²⁺-calmodulin inhibits Ca²⁺ release mediated by types 1, 2 and 3 inositol trisphosphate receptors. Biochem. J. 345, 357-363.
• Rosenberg, HJ, Riley, AM, Correa, V, Taylor, CW & Potter, BVL (2000) C-Glycoside based mimics of D-myo-inositol-1,4,5-trisphosphate. Carbohydr. Res. 329, 7-16.
• De Kort, M, Correa, V, Valentijn, ARPM, Potter, BVL, Taylor, CW & van Boom, JH (2000) Synthesis of potent agonists of the D-myo-inositol 1,4,5-trisphosphate receptor based on clustered disaccharide polyphosphate analogs of adenophostin A. J. Med. Chem. 43, 3295-3303.
• Short, AD, Winston, GP & Taylor, CW (2000) Different receptors use inositol trisphosphate to mobilize Ca²⁺ from different intracellular pools. Biochem. J. 351, 683-686.
• Adkins, CE, Wissing, F, Potter, BVL & Taylor, CW (2000) Rapid activation and partial inactivation of inositol trisphosphate receptors by adenophostin A. Biochem. J. 352, 929-933.
• Tasker, PN, Taylor, CW & Nixon, GF (2000) Changes in expression and distribution of inositol 1,4,5-trisphosphate receptor subtypes following primary culture of vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 273, 907-912.
• Marwood, RD, Jenkins, DJ, Correa, V, Taylor, CW & Potter, BVL (2000) Contribution of the adenine base to the activity of adenophostin A investigated using a base replacement strategy. J. Med. Chem. 43, 4278-4287.

1999

• Beecroft, MD, Marchant, JS, Riley, AM, Van Straten, NCR, Van der Marel, GA, Van Boom, JH, Potter, BVL & Taylor, CW (1999) Acyclophostin: A ribose-modified analog of adenophostin A with high affinity for inositol 1,4,5-trisphosphate receptors and pH-dependent efficacy. Mol. Pharmacol. 55, 109-117.
• McKillen, K, Thornton, S & Taylor, CW (1999) Oxytocin selectively increases the intracellular calcium sensitivity of myometrium during the falling phase of phasic contractions. Am. J. Physiol. 276, E345-E351.
• Broad, L, Cannon, TR & Taylor, CW (1999) A non-capacitative pathway activated by arachidonic acid is the major Ca²⁺ entry in A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J.Physiol 517.1, 121-134.
• McNulty, TJ & Taylor, CW (1999) A plasma membrane receptor for heavy metal ions stimulates Ca²⁺ mobilization in hepatocytes. Biochem. J. 339, 555-561.
• Morris, SA, Correa, V, Cardy, TJA, O?Beirne, G & Taylor CW (1999) Interactions between inositol trisphosphate receptors and fluorescent Ca²⁺ indicators. Cell Calcium 25, 137-142.
• Marwood, RD, Riley, AM, Correa, V, Taylor, CW & Potter, BVL (1999) Simplification of adenophostin A defines a minimal s structure for potent glucopyraonoside-based mimics of d-myo-inositol 1,4,5-trisphosphate. Bioorg. Med. Chem. Lett. 9, 453-458.
• Snitsarev, VA & Taylor, CW (1999) Overshooting cytosolic Ca²⁺ signals evoked by capacitative Ca²⁺ entry result from delayed stimulation of a plasma membrane Ca²⁺ pump. Cell Calcium. 25, 409-417.
• Broad, LM, Cannon, TR, Short, AD & Taylor, CW (1999) Receptors linked to polyphosphoinositide hydrolysis stimulate Ca²⁺ extrusion by a phospholipase C-independent mechanism. Biochem. J. 342, 199-206.
• Felemez, M, Schlewer, G, Jenkins, DJ, Correa, V, Taylor, CW, Potter, BVL & Spiess, B. Inframolecular studies of the protonation of 1D-1,2,3/3,5-cyclopentanepentaol 1,3,4-trisphosphate, a ring contacted analogue of 1 D-myo-inositol 1,4,5-trisphosphate. Carbohydrate Research 322, 95-101.
• Swatton, JE, Morris, SA, Cardy, TJA & Taylor, CW (1999) Type 3 inositol trisphosphate receptors in RINm5F cells are biphasically regulated by cytosolic Ca²⁺ and mediate quantal Ca²⁺ mobilization. Biochem. J. 344, 55-60.
• Adkins, CE & Taylor, CW (1999) Lateral inhibition of inositol trisphophate receptors by cytosolic calcium. Curr. Biol. 9, 1115-1118.
• Taylor, CW & Marchant, JS (1999) Measuring inositol 1,4,5-trisphosphate-evoked 45 Ca²⁺ release from intracellular stores. In Signal Transduction: A Practical Approach. IRL Press, Oxford. pp361-384.
• Taylor, CW, Genazzani, AA & Morris, SA (1999) Expression of inositol trisphosphate receptors. Cell Calcium. 26, 237-251.
• Taylor CW (1999) Measuring Ca²⁺ fluxes in permeabilized cells. In Calcium Signaling (Ed. J W Putney), CRC Press, Boca Raton, USA. pp111-130.

1998

• Ukhanov, K, Ukhanova, M, Taylor, CW & Payne, R (1998) Putative inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in Limulus photoreceptors. Neuroscience 86, 23-28.
• Marchant, JS & Taylor, CW (1998) Rapid activation and partial inactivation of inositol trisphosphate receptors by inositol trisphosphate. Biochemistry 37, 11524-11533.
• Cardy, TJA & Taylor, CW (1998) A novel role for calmodulin: Ca²⁺-independent inhibition of type 1 inositol trisphosphate receptors. Biochem. J. 334, 447-455.
• Beecroft, MD & Taylor, CW (1998) Luminal Ca²⁺ regulates passive Ca²⁺ efflux from the intracellular stores of hepatocytes. Biochem. J. 334, 431-435.
• Taylor CW & Broad, L (1998) Pharmacological analysis of intracellular Ca²⁺ signalling: problems and pitfalls. Trends Pharmacol. Sci. 19, 370-375.
• Taylor CW (1998) Inositol trisphosphate receptors: Ca²⁺-modulated intracellular Ca²⁺ channels. Biochem. Biophys. Acta. 1426, 19-33.
• Taylor, CW (1998) Intracellular Ca²⁺ channels. In The RBI Handbook of Receptor Classification and Signal Transduction. Third edition, edited by K Watling. pp142-143.

1997

• Madge, L, Marshall, ICB & Taylor, CW (1997) Delayed autoregulation of the Ca²⁺ signals resulting from Ca²⁺ entry in bovine pulmonary artery endothelial cells. J. Physiol. 498.2, 351-369.
• Marchant, JS, Chang, Y-T, Chung, S-K, Irvine, RF & Taylor, CW (1997) Rapid kinetic measurements of 45 Ca²⁺ mobilization reveal that Ins(2,4,5)P3 is a partial agonist at hepatic InsP3 receptors. Biochem. J. 321, 573-576.
• Beecroft, MD & Taylor, CW (1997) Incremental Ca²⁺ mobilization by inositol trisphosphate receptors is unlikely to depend on their desensitization or regulation by luminal or cytosolic Ca²⁺. Biochem. J. 326, 215-220.
• Marchant, JS & Taylor, CW (1997) Cooperative activation of IP₃ receptors by sequential binding of IP₃ and Ca²⁺ safeguards against spontaneous activity. Current Biol. 7, 510-518.
• Patel, S, Morris, SA, Adkins, CE, O?Beirne, G & Taylor, CW (1997) Ca²⁺-independent inhibition of inositol trisphosphate receptors by calmodulin: redistribution of calmodulin as a possible means of regulating Ca²⁺ mobilization. Proc. Natl. Acad. Sci. USA 94, 11627-11632.
• Marchant, JS, Beecroft, MD, Riley, AM, Jenkins, JJ, Marwood, RD, Taylor, CW & Potter, BVL (1997) Disaccharide polyphosphates based upon adenophostin A activate hepatic d-myo-inositol 1,4,5-trisphosphate receptors. Biochemistry 36, 12780-12790.
• Cardy, TJA, Traynor, D & Taylor, CW (1997) Differential regulation of types 1 and 3 inositol trisphosphate receptors by cytosolic Ca²⁺. Biochem. J. 328, 785-793.

Some Oldies

• Taylor, CW & Traynor, D (1995) Calcium and inositol trisphosphate receptors. J. Membr. Biol. 145, 109-118.
• Taylor, CW (1995) Why do hormones stimulate Ca²⁺ mobilization? Biochem. Soc. Trans. 23, 637-642.
• Combettes, L, Cheek, TR & Taylor, CW (1996) Regulation of inositol trisphosphate receptors by luminal Ca²⁺ contributes to quantal Ca²⁺ mobilisation. EMBO. J. 15, 2086-2093.
• Dasso, LLT & Taylor, CW (1994) Interactions between Ca²⁺-mobilizing receptors and their G proteins in hepatocytes. J. Biol. Chem. 269, 8647-8652.
• Marshall, ICB & Taylor CW (1994) Two calcium-binding sites mediate the interconversion of liver inositol 1,4,5-trisphosphate receptors between three conformational states. Biochem. J. 301, 591-598
• Hargreaves, AC, Lummis, SCR & Taylor, CW (1994) Ca²⁺ permeability of cloned and native 5-HT3 receptors. Mol. Pharmacol. 46, 1120-1128.
• Byron, KL & Taylor, CW (1993) Spontaneous Ca²⁺ spikes in A7r5 cells do not require mobilization of intracellular Ca²⁺ stores. J. Biol. Chem. 268, 6945-6952.
• Marshall, ICB & Taylor, CW (1993) Biphasic effects of cytosolic Ca²⁺ on Ins(1,4,5)P3-stimulated Ca²⁺ mobilization in hepatocytes. J. Biol. Chem. 268, 13214-13220.
• Nunn, DL & Taylor, CW (1992) Luminal Ca²⁺ increases the sensitivity of Ca²⁺ stores to inositol 1,4,5-trisphosphate. Mol. Pharmacol. 41, 115-119.
• Oldershaw, KA, Richardson, A & Taylor, CW (1992) Prolonged exposure to inositol 1,4,5-trisphosphate does not cause intrinsic desensitization of the intracellular Ca²⁺-mobilizing receptor. J. Biol. Chem. 267, 16312-16316.
• Dasso, LLT & Taylor, CW (1992) Different Ca²⁺-mobilizing receptors share the same G protein pool in hepatocytes. Mol. Pharmacol. 42, 453-457.
• Taylor, CW (1992) Kinetics of inositol 1,4,5-trisphosphate-stimulated Ca²⁺ mobilization. Adv. Second Messenger Phosphoprotein Res.26, 109-142.
• Taylor, CW & Marshall, ICB (1992) Calcium and inositol 1,4,5-trisphosphate receptors: a complex relationship. Trends Biochem. Sci. 17, 403-407.
• Missiaen, L, Taylor, CW & Berridge, MJ (1991) Spontaneous calcium release from inositol 1,4,5-trisphosphate-sensitive calcium stores. Nature 352, 241-244.
• Taylor, CW & Richardson, A (1991) Structure and function of inositol 1,4,5-trisphosphate receptors. Pharmac. Ther.51, 97-137.
• Nunn, DL, Potter, BVL & Taylor, CW (1990) Molecular target size of inositol trisphosphate receptors in cerebellum and liver. Biochem. J. 265, 393-398.
• Taylor, CW & Potter, BVL (1990) The size of the inositol 1,4,5-trisphosphate-sensitive Ca²⁺ pool depends on inositol trisphosphate concentration. Biochem. J. 266, 189-194.
• Taylor, CW (1990) The role of G proteins in transmembrane signalling. Biochem. J. 272, 1-13.
• Merritt, JE, Taylor, CW, Rubin, RP & Putney, JW Jr. (1986) Evidence suggesting that a novel guanine nucleotide-dependent regulatory protein couples receptors to phospholipase C in exocrine pancreas. Biochem. J. 236, 337-343.
• Taylor, CW (1986) Calcium regulation in insects. Adv. Insect Physiol. 19, 155-186.
• Taylor, CW & Merritt, JE (1986) Receptor coupling to polyphosphoinositide turnover: a parallel with the adenylate cyclase system. Trends Pharmacol. Sci. 7, 238-242.
• Taylor, CW (1985) Calcium regulation in vertebrates: an overview. Comp. Biochem. Physiol. 82A, 249-255.