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Structure and function of calcium signalling pathways

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Professor Colin W. Taylor

E-Mail: cwt1000@cam.ac.uk

Tel: +44 1223 334058/334062

 

Keywords

Calcium, cell signalling, endoplasmic reticulum, IP3 receptor, ion channel, lysosome, migration, protein structure, protein trafficking.

Lab members

Philippa Dale - - Mike Keebler - Vera Konieczny - Abha Meena - - Dr. Dave Prole - Dr. Ana Rossi - Huma Saleem - Dr. Nadia Shah - Dr. Emily Taylor - Dr. Steve Tovey

Research summary

All cells must sense their surroundings and communicate with each other. Receptors in the plasma membrane are the antennae that detect extracellular signals, and they communicate with the cell interior via intracellular messengers. Calcium ions (Ca2+), the simplest of these intracellular messengers, are used to regulate almost every cellular behaviour from fertilization to cell death. Most messengers are synthesized and degraded on-demand, but calcium is an element and so its concentration can only be regulated by moving it into and out of the cytosol across membranes. Most receptors that evoke Ca2+ signals do so by stimulating Ca2+-permeable ion channels to open, allowing Ca2+ to flow rapidly down its concentration gradient into the cytosol. Our work is primarily concerned with the most important and widely expressed of these Ca2+ channels, IP3 receptors. These reside largely within the membranes of the endoplasmic reticulum and they  initiate the Ca2+ signals evoked by the many receptors that stimulate formation of IP3. We are currently addressing four major questions:

  • How does binding of IP3 to a channel, the IP3 receptor, that is five-thousand times larger than IP3 cause the channel to open?
  • How are signalling pathways organized to allow delivery of IP3 and other messengers to IP3 receptors?
  • How does the mobility of intracellular organelles and proteins within them contribute to the Ca2+ signals evoked by IP3?
  • How do cells decode spatially organized Ca2+ signals?

Key references

  • Saraiva, N., Prole, DL, Carrara, G, Johnson, BF, Taylor, CW, Parsons, M & Smith, GL (2013) hGAAP promotes cell adhesion and migration via the stimulation of store-operated Ca2+ entry and calpain 2. J. Cell. Biol. 202, 699-713.
  • Seo, M-D, Velamakanni, S, Ishiyama, N, Stathopulos, PB, Rossi, AM, Khan, SA, Dale, P, Li, C, Ames, JB, Ikura, M & Taylor, CW (2012) Structural and functional conservation of key domains in InsP3 and ryanodine receptors. Nature 483, 108-112.
  • Rahman, T-U, Skupin, A, Falcke, M & Taylor CW (2009) Clustering of IP3 receptors by IP3 retunes their regulation by IP3 and Ca2+. Nature. 458, 655-659.
  • Tovey, SC, Dedos, SG, Taylor, EJA, Church, JE & Taylor CW (2008) Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP. J. Cell Biol. 183, 297-311.