First Author | Leshchyns'ka I | Year | 2006 |
Journal | Neuron | Volume | 52 |
Issue | 6 | Pages | 1011-25 |
PubMed ID | 17178404 | Mgi Jnum | J:117227 |
Mgi Id | MGI:3695838 | Doi | 10.1016/j.neuron.2006.10.020 |
Citation | Leshchyns'ka I, et al. (2006) The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron 52(6):1011-25 |
abstractText | 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. |