Endocytic scaffold Intersectin 1 regulates vesicle reclustering in the reserve pool of the giant vertebrate synapse

Олег Викторович Шупляков, Kristin Fredrich, Arndt Pechstein, Fabian Gerth, Olga Vorontsova, Елена Сергеевна Сопова, Ольга Михайловна Коренькова, Volker Haucke, Christian Freund

Research output

Abstract

Synaptic vesicles (SVs) are accumulated at active zones in clusters, which are comprised of ready-releasable and reserve pools. Phosphoprotein synapsin I plays critical role in organizing SVs in the reserve pool in many central synapses. SVs in the reserve pool replenish the ready-releasable pool to sustain neurotransmission during high-rate activity and are rapidly reclustered after stimulation. How these SV trafficking events are regulated is largely unknown. Using the giant reticulospinal model synapse in lamprey we show that the scaffolding protein intersectin 1 (ITSN1) regulates the synapsin 1 function during synaptic activity by forming a dynamic complex with synapsin. Like in mammalian synapses ITSN1 is a component of an extravesicular matrix of the reserve pool of SVs in giant lamprey synapses. The complex formation with synapsin 1 is mediated by SH3A (Src-homology 3 A) domain of ITSN1, which binds to the D domain of synapsin I. An intramolecular switch within ITSN1 regulates the interaction between the proteins. Microinjection of antibodies against SH3A domain into giant synapses at rest does not perturb SV organization, while during stimulation it disrupts the vesicle clustering in the reserve pool thus supporting that ITSN1 and synapsin 1 come into interaction during synaptic activity. Our data suggest that the SH3A domain of ITSN1 serves to sequester synapsin 1 within the reserve pool when it dissociates from SV during stimulation and promotes efficient reclustering when stimulation ceased by releasing dephosphorylated synapsin within the reserve pool. Thus, our experiments uncover the molecular mechanism regulating vesicle reclustering within the reserve pool of SVs.
Acknowledgements: This work was supported by the Swedish Research Council Grants VRM N01501 and Russian Science Foundation N16-15-10273 (to O.S.), by German Research Foundation Grants SFB958/A07 and -/Z03 (to C.F. and V.H.), and NeuroCure Cluster of Excellence Grant Exc-257 (to V.H.).
Original languageEnglish
Pages2018-S-1926-SfN
Number of pages1
Publication statusPublished - 2018
EventSociety for Neuroscience Meeting - San Diego
Duration: 3 Nov 20187 Nov 2018

Conference

ConferenceSociety for Neuroscience Meeting
Abbreviated titleSFN 2018
CountryUnited States
CitySan Diego
Period3/11/187/11/18

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