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Department of Pharmacology

 
Read more at: Direct observation of aggregate-triggered selective autophagy in human cells.

Direct observation of aggregate-triggered selective autophagy in human cells.

Degradation of aggregates by selective autophagy is important as damaged proteins may impose a threat to cellular homeostasis. Although the core components of the autophagy machinery are well characterized, the spatiotemporal regulation of many selective autophagy processes, including aggrephagy, remains largely unexplored. Furthermore, because most live-cell imaging studies have so far focused on starvation-induced autophagy, little is known about the dynamics of aggrephagy.


Read more at: HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.

HSV-1 Glycoproteins Are Delivered to Virus Assembly Sites Through Dynamin-Dependent Endocytosis.

Herpes simplex virus-1 (HSV-1) is a large enveloped DNA virus that belongs to the family of Herpesviridae. It has been recently shown that the cytoplasmic membranes that wrap the newly assembled capsids are endocytic compartments derived from the plasma membrane. Here, we show that dynamin-dependent endocytosis plays a major role in this process. Dominant-negative dynamin and clathrin adaptor AP180 significantly decrease virus production.


Read more at: Three-Step Model for Polarized Sorting of KIF17 into Dendrites.

Three-Step Model for Polarized Sorting of KIF17 into Dendrites.

Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11].


Read more at: Design and self-assembly of simple coat proteins for artificial viruses.

Design and self-assembly of simple coat proteins for artificial viruses.

Viruses are among the simplest biological systems and are highly effective vehicles for the delivery of genetic material into susceptible host cells. Artificial viruses can be used as model systems for providing insights into natural viruses and can be considered a testing ground for developing artificial life. Moreover, they are used in biomedical and biotechnological applications, such as targeted delivery of nucleic acids for gene therapy and as scaffolds in material science.


Read more at: Myosin-V Induces Cargo Immobilization and Clustering at the Axon Initial Segment.

Myosin-V Induces Cargo Immobilization and Clustering at the Axon Initial Segment.

The selective transport of different cargoes into axons and dendrites underlies the polarized organization of the neuron. Although it has become clear that the combined activity of different motors determines the destination and selectivity of transport, little is known about the mechanistic details of motor cooperation. For example, the exact role of myosin-V in opposing microtubule-based axon entries has remained unclear. Here we use two orthogonal chemically-induced heterodimerization systems to independently recruit different motors to cargoes.


Read more at: Probing aggrephagy using chemically-induced protein aggregates.

Probing aggrephagy using chemically-induced protein aggregates.

Selective types of autophagy mediate the clearance of specific cellular components and are essential to maintain cellular homeostasis. However, tools to directly induce and monitor such pathways are limited. Here we introduce the PIM (particles induced by multimerization) assay as a tool for the study of aggrephagy, the autophagic clearance of aggregates. The assay uses an inducible multimerization module to assemble protein clusters, which upon induction recruit ubiquitin, p62, and LC3 before being delivered to lysosomes.


Read more at: Local structural dynamics of alpha-synuclein correlate with aggregation in different physiological conditions

Local structural dynamics of alpha-synuclein correlate with aggregation in different physiological conditions

<jats:title>ABSTRACT</jats:title><jats:p>In Parkinson’s disease and other synucleinopathies, the intrinsically disordered, presynaptic protein alpha-synuclein misfolds and aggregates. We hypothesise that the exposure of alpha-synuclein to different cellular environments, with different chemical compositions, pH and binding partners, alters its biological and pathological function by inducing changes in molecular conformation.


Read more at: Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of monomeric conformations is difficult. Herein, we used the biologically relevant calcium ion to investigate the conformation of monomeric aSyn in relation to its aggregation propensity.


Read more at: The Cellular Environment Affects Monomeric α-Synuclein Structure

The Cellular Environment Affects Monomeric α-Synuclein Structure

Thepresynapticproteina-synuclein(aSyn)isan‘intrinsicallydisorderedprotein’thatishighlydynamicinconformation.TransientintramolecularinteractionsbetweenitschargedNandCtermini,andbetweenitshydrophobicregionandtheCterminus,preventself-association.Theseinteractionsinhibittheformationofinsolubleinclusions,whicharethepathologicalhallmarkofParkinson’sdiseaseandmanyothersynucleinopathies.ThisreviewdiscusseshowtheseintramolecularinteractionsareinfluencedbythespecificenvironmentaSynisin.Wediscusshowcharge,pH,calcium,andsaltaffectthephysiologicalstructureofmonomericaSyn,andhowtheymayfavourtheformationo


Read more at: Sequential high gravity ethanol fermentation and anaerobic digestion of steam explosion and organosolv pretreated corn stover.

Sequential high gravity ethanol fermentation and anaerobic digestion of steam explosion and organosolv pretreated corn stover.

The present work investigates the suitability of pretreated corn stover (CS) to serve as feedstock for high gravity (HG) ethanol production at solids-content of 24wt%. Steam explosion, with and without the addition of H2SO4, and organosolv pretreated CS samples underwent a liquefaction/saccharification step followed by simultaneous saccharification and fermentation (SSF). Maximum ethanol concentration of ca. 76g/L (78.3% ethanol yield) was obtained from steam exploded CS (SECS) with 0.2% H2SO4. Organosolv pretreated CS (OCS) also resulted in high ethanol concentration of ca.