Coordinated bi-directional trafficking of synaptic vesicle and active zone proteins in peripheral nerves

dc.contributor.authorJuranek, Judyta K.en
dc.contributor.authorMukherjee, Konarken
dc.contributor.authorJahn, Reinharden
dc.contributor.authorLi, Jia-Yien
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-07-21T17:46:10Zen
dc.date.available2021-07-21T17:46:10Zen
dc.date.issued2021-06-25en
dc.description.abstractSynaptic transmission is mediated by neurotransmitters that are stored in synaptic vesicles (SV) and released at the synaptic active zone (AZ). While in recent years major progress has been made in unraveling the molecular machinery responsible for SV docking, fusion and exocytosis, the mechanisms governing AZ protein and SV trafficking through axons still remain unclear. Here, we performed stop flow nerve ligation to examine axonal trafficking of endogenous AZ and SV proteins. Rat sciatic nerves were collected 1 h, 3 h and 8 h post ligation and processed for immunohistochemistry and electron microscopy. First, we followed the transport of an integral synaptic vesicle protein, SV2A and a SVassociated protein involved in SV trafficking, Rab3a, and observed that while SV2A accumulated on both sides of ligation, Rab3a was only noticeable in the proximal segment of the ligated nerve indicating that only SV trans-membrane protein SV2A displayed a bi-directional axonal transport. We then demonstrate that multiple AZ proteins accumulate rapidly on either side of the ligation with a timescale similar to that of SV2A. Overall, our data uncovers an unexpected robust bi-directional, coordinated-trafficking of SV and AZ proteins in peripheral nerves. This implies that pathological disruption of axonal trafficking will not only impair trafficking of newly synthesized proteins to the synapse but will also affect retrograde transport, leading to neuronal dysfunction and likely neurodegeneration. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en
dc.description.notesEMBO short term fellowship awarded to JKJ and institutional funding provided by RJ and JL covered all expenses related to study design and conduction of the experiments designed in the study.en
dc.description.sponsorshipEMBOEuropean Molecular Biology Organization (EMBO)en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.bbrc.2021.04.041en
dc.identifier.eissn1090-2104en
dc.identifier.issn0006-291Xen
dc.identifier.pmid33933994en
dc.identifier.urihttp://hdl.handle.net/10919/104248en
dc.identifier.volume559en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectActive zoneen
dc.subjectSynaptic vesicleen
dc.subjectPresynapseen
dc.subjectMotor neuronen
dc.subjectSciatic nerveen
dc.titleCoordinated bi-directional trafficking of synaptic vesicle and active zone proteins in peripheral nervesen
dc.title.serialBiochemical and Biophysical Research Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen
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