1. The Adhesion Molecule CHL1 Regulates Uncoating of Clathrin-Coated Synaptic Vesicles
- Author
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Leshchyns'ka, Iryna, Sytnyk, Vladimir, Richter, Melanie, Andreyeva, Aksana, Puchkov, Dmytro, and Schachner, Melitta
- Subjects
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ADENOSINE triphosphatase , *CELL membranes , *ABSORPTION (Physiology) - Abstract
Summary: In searching for binding partners of the intracellular domain of the immunoglobulin superfamily adhesion molecule CHL1, we identified the clathrin-uncoating ATPase Hsc70. CHL1 gene ablation resulted in reduced targeting of Hsc70 to the synaptic plasma membrane and synaptic vesicles, suggesting CHL1 as a synapse-targeting cue for Hsc70. CHL1 accumulates in presynaptic membranes and, in response to synapse activation, is targeted to synaptic vesicles by endocytosis. CHL1 deficiency or disruption of the CHL1/Hsc70 complex results in accumulation of abnormally high levels of clathrin-coated synaptic vesicles with a reduced ability to release clathrin. Generation of new clathrin-coated synaptic vesicles in an activity-dependent manner is inhibited when the CHL1/Hsc70 complex is disrupted, resulting in impaired uptake and release of FM dyes in synaptic boutons. Abnormalities in clathrin-dependent synaptic vesicle recycling may thus underlie brain malfunctions in humans and mice that carry mutations in the CHL1 gene. [Copyright &y& Elsevier]
- Published
- 2006
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