Intersectin associates with synapsin and regulates its nanoscale localization and function
| Autor: | Maria Jäpel, Christian Freund, Fabian Gerth, Franco Onofri, Volker Haucke, Fabio Benfenati, Dmytro Puchkov, Gaga Kochlamazashvili, Martin Lehmann, Tanja Maritzen, Alexander G. Nikonenko, Kristin Fredrich, Oleg Shupliakov, Arndt Pechstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Scaffold protein Synapsin I Endocytic cycle Biology Neurotransmission Bioinformatics Hippocampus Synaptic Transmission Corrections Synaptic vesicle Exocytosis Mice 03 medical and health sciences 0302 clinical medicine Animals Active zone Neurons Neurotransmitter Agents Multidisciplinary synaptic vesicles neurotransmission multidomain scaffold NMR spectroscopy intramolecular regulation Synapsin Intersectin-1 Synapsins Endocytosis Cell biology Mice Inbred C57BL Adaptor Proteins Vesicular Transport 030104 developmental biology nervous system Synapses Synaptic Vesicles 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 114(45):12057-12062 |
| Popis: | Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery. |
| Databáze: | OpenAIRE |
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