PICK1 targets activated protein kinase Cα to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2

Perez, J. L., Khatri, L., Chang, C., Srivastava, S., Osten, P., Ziff, E. B. (2001) PICK1 targets activated protein kinase Cα to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. Journal of Neuroscience, 21 (15). pp. 5417-5428. ISSN 02706474 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/11466413

Abstract

The PICK1 protein interacts in neurons with the AMPA-type glutamate receptor subunit 2 (GluR2) and with several other membrane receptors via its single PDZ domain. We show that PICK1 also binds in neurons and in heterologous cells to protein kinase Cα (PKCα) and that the interaction is highly dependent on the activation of the kinase. The formation of PICK1-PKCα complexes is strongly induced by TPA, and PICK1-PKCα complexes are cotargeted with PICK1-GluR2 complexes to spines, where GluR2 is found to be phosphorylated by PKC on serine 880. PICK1 also reduces the plasma membrane levels of the GluR2 subunit, consistent with a targeting function of PICK1 and a PKC-facilitated release of GluR2 from the synaptic anchoring proteins ABP and GRIP. This work indicates that PICK1 functions as a targeting and transport protein that directs the activated form of PKCα to GluR2 in spines, leading to the activity-dependent release of GluR2 from synaptic anchor proteins and the PICK1-dependent transport of GluR2 from the synaptic membrane.

Item Type: Paper
Uncontrolled Keywords: Endocytosis GluR2 PDZ domain PICK1 PKCα Spine AMPA receptor animal cell article enzyme activation hippocampus nonhuman priority journal protein targeting protein transport rat synaptic transmission 3T3 Cells Animals Carrier Proteins Cells, Cultured Cricetinae Dimerization Enzyme Activators Humans Isoenzymes Macromolecular Substances Mice Models, Molecular Mutagenesis, Site-Directed Neurons Nuclear Proteins Protein Binding Protein Kinase C Protein Kinase C-alpha Rats Receptor Aggregation Receptors, AMPA Tetradecanoylphorbol Acetate Transfection Two-Hybrid System Techniques
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: Matt Covey
Date Deposited: 05 Apr 2013 01:48
Last Modified: 05 Apr 2013 01:48
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28098

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