PACSIN1 regulates the dynamics of AMPA receptor trafficking

Widagdo, Jocelyn, Fang, Huaqiang, Jang, Se Eun and Anggono, Victor (2016) PACSIN1 regulates the dynamics of AMPA receptor trafficking. Scientific Reports, 6 31070: 1-9. doi:10.1038/srep31070

Author Widagdo, Jocelyn
Fang, Huaqiang
Jang, Se Eun
Anggono, Victor
Title PACSIN1 regulates the dynamics of AMPA receptor trafficking
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-08-04
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep31070
Open Access Status DOI
Volume 6
Issue 31070
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract Dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses plays an important role in synaptic plasticity. We previously reported that the protein kinase C and casein kinase II substrate in neurons (PACSIN) forms a complex with AMPARs through its interaction with the protein interacting with C-kinase 1 (PICK1) to regulate NMDA receptor (NMDAR)-induced AMPAR endocytosis and cerebellar long-term depression. However, the molecular mechanism by which PACSIN regulates the dynamics of AMPAR trafficking remains unclear. Using a pH-sensitive green fluorescent protein, pHluorin, tagged to the extracellular domain of the GluA2 subunit of AMPARs, we demonstrate dual roles for PACSIN1 in controlling the internalization and recycling of GluA2 after NMDAR activation. Structure and function analysis reveals a requirement for the PACSIN1 F-BAR and SH3 domains in controlling these NMDAR-dependent processes. Interestingly, the variable region, which binds to PICK1, is not essential for NMDAR-dependent GluA2 internalization and is required only for the correct recycling of AMPARs. These results indicate that PACSIN is a versatile membrane deformation protein that links the endocytic and recycling machineries essential for dynamic AMPAR trafficking in neurons.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 477108
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Tue, 09 Aug 2016, 22:32:17 EST by Victor Anggono on behalf of Clem Jones Centre for Ageing Dementia Research