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Publication : Fast neurotransmitter release regulated by the endocytic scaffold intersectin.

First Author  Sakaba T Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  20 Pages  8266-71
PubMed ID  23633571 Mgi Jnum  J:197322
Mgi Id  MGI:5492178 Doi  10.1073/pnas.1219234110
Citation  Sakaba T, et al. (2013) Fast neurotransmitter release regulated by the endocytic scaffold intersectin. Proc Natl Acad Sci U S A 110(20):8266-71
abstractText  Sustained fast neurotransmission requires the rapid replenishment of release-ready synaptic vesicles (SVs) at presynaptic active zones. Although the machineries for exocytic fusion and for subsequent endocytic membrane retrieval have been well characterized, little is known about the mechanisms underlying the rapid recruitment of SVs to release sites. Here we show that the Down syndrome-associated endocytic scaffold protein intersectin 1 is a crucial factor for the recruitment of release-ready SVs. Genetic deletion of intersectin 1 expression or acute interference with intersectin function inhibited the replenishment of release-ready vesicles, resulting in short-term depression, without significantly affecting the rate of endocytic membrane retrieval. Acute perturbation experiments suggest that intersectin-mediated vesicle replenishment involves the association of intersectin with the fissioning enzyme dynamin and with the actin regulatory GTPase CDC42. Our data indicate a role for the endocytic scaffold intersectin in fast neurotransmitter release, which may be of prime importance for information processing in the brain.
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