Fast neurotransmitter release regulated by the endocytic scaffold intersectin.

Abstract

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.

• Authors: Takeshi Sakaba, Natalia L Kononenko, Jelena Bacetic, Arndt Pechstein, Jan Schmoranzer, Lijun Yao, Holger Barth, Oleg Shupliakov, Oliver Kobler, Klaus Aktories, Volker Haucke
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 20 Pg. 8266-71 (May 14 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23633571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Vesicular Transport
• Neurotransmitter Agents
• Peptides
• intersectin 1
• cdc42 GTP-Binding Protein

Topics

• Adaptor Proteins, Vesicular Transport (metabolism)
• Animals
• Brain (metabolism)
• Brain Stem (metabolism)
• Endocytosis
• Gene Deletion
• Gene Expression Regulation
• Mice
• Mice, Knockout
• Microscopy, Confocal
• Neurotransmitter Agents (metabolism)
• Peptides (chemistry)
• Protein Structure, Tertiary
• Rats
• Rats, Wistar
• Synapses (metabolism)
• Synaptic Transmission
• Synaptic Vesicles (metabolism)
• cdc42 GTP-Binding Protein (metabolism)