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

Title
 PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A.
Authors
 Suk Jin Ko; Kaname Isozaki; Katherine W. Roche; Chul Hoon Kim; Dong Goo Kim; Steven Park; So Ra Oh; Sun Young Sohn; Ho Jin Cho; Jeong Ho Lee; Insook Kim
Issue Date
2012
Journal Title
 Journal of Neuroscience
ISSN
 0270-6474
Citation
 Journal of Neuroscience, Vol.32(46) : 16391~16401, 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
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/91001
DOI
10.1523/JNEUROSCI.1964-12.2012
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
Yonsei Authors
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