The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors.

Abstract:

:The formation, function, and plasticity of synapses require dynamic changes in synaptic receptor composition. Here, we identify the sorting receptor SorCS1 as a key regulator of synaptic receptor trafficking. Four independent proteomic analyses identify the synaptic adhesion molecule neurexin and the AMPA glutamate receptor (AMPAR) as major proteins sorted by SorCS1. SorCS1 localizes to early and recycling endosomes and regulates neurexin and AMPAR surface trafficking. Surface proteome analysis of SorCS1-deficient neurons shows decreased surface levels of these, and additional, receptors. Quantitative in vivo analysis of SorCS1-knockout synaptic proteomes identifies SorCS1 as a global trafficking regulator and reveals decreased levels of receptors regulating adhesion and neurotransmission, including neurexins and AMPARs. Consequently, glutamatergic transmission at SorCS1-deficient synapses is reduced due to impaired AMPAR surface expression. SORCS1 mutations have been associated with autism and Alzheimer disease, suggesting that perturbed receptor trafficking contributes to synaptic-composition and -function defects underlying synaptopathies.

journal_name

Neuron

journal_title

Neuron

authors

Savas JN,Ribeiro LF,Wierda KD,Wright R,DeNardo-Wilke LA,Rice HC,Chamma I,Wang YZ,Zemla R,Lavallée-Adam M,Vennekens KM,O'Sullivan ML,Antonios JK,Hall EA,Thoumine O,Attie AD,Yates JR 3rd,Ghosh A,de Wit J

doi

10.1016/j.neuron.2015.08.007

subject

Has Abstract

pub_date

2015-08-19 00:00:00

pages

764-80

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(15)00682-0

journal_volume

87

pub_type

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