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)
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: |
2001 |
| Date Deposited: |
05 Apr 2013 01:48 |
| Last Modified: |
05 Apr 2013 01:48 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/28098 |
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