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PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A.

Authors
 Suk Jin Ko  ;  Kaname Isozaki  ;  Insook Kim  ;  Jeong Ho Lee  ;  Ho Jin Cho  ;  Sun Young Sohn  ;  So Ra Oh  ;  Steven Park  ;  Dong Goo Kim  ;  Chul Hoon Kim  ;  Katherine W. Roche 
Citation
 JOURNAL OF NEUROSCIENCE, Vol.32(46) : 16391-16401, 2012 
Journal Title
 JOURNAL OF NEUROSCIENCE 
ISSN
 0270-6474 
Issue Date
2012
Abstract
Glutamate is the major excitatory neurotransmitter in the mammalian CNS and acts on both ionotropic and metabotropic glutamate receptors (mGluRs). The mGluRs are widely distributed in the CNS and modulate a variety of neuronal processes, including neurotransmitter release and ion channel function. In hippocampus and cortex, mGluR5 is highly expressed and plays an important role in the regulation of synaptic plasticity. Calmodulin (CaM) binding dynamically regulates mGluR5 surface expression; however, the mechanisms linking CaM to mGluR5 trafficking are not clear. Recent studies showed that CaM binding to mGluR7 regulates its trafficking in a phosphorylation-dependent manner by disrupting the binding of protein interacting with C kinase 1. The E3 ligase seven in absentia homolog (Siah)-1A binds to mGluR5 and competes with CaM binding, making it an intriguing molecule to regulate phosphorylation-dependent trafficking of mGluR5. In the present study, we find that CaM competes with Siah-1A for mGluR5 binding in a phosphorylation-dependent manner in rat hippocampal neurons. Specifically, phosphorylation of mGluR5 S901 favors Siah-1A binding by displacing CaM. We identified critical residues regulating Siah-1A binding to mGluR5 and showed that binding is essential for the Siah-1A effects on mGluR5 trafficking. Siah-1A binding decreases mGluR5 surface expression and increases endosomal trafficking and lysosomal degradation of mGluR5. Thus CaM-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking. These findings support a conserved role for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor-binding proteins
Files in This Item:
T201204091.pdf Download
DOI
10.1523/JNEUROSCI.1964-12.2012
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Ko, Suk Jin(고석진)
Kim, Dong Goo(김동구)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Sohn, Sun Young(손선영)
Oh, So Ra(오소라)
Cho, Hojin(조호진) ORCID logo https://orcid.org/0000-0002-8686-172X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91001
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