Abstract
PICK1 and ABP/GRIP bind to the AMPA receptor (AMPAR) GluR2 subunit C terminus. Transfer of the receptor from ABP/GRIP to PICK1, facilitated by GluR2 S880 phosphorylation, may initiate receptor trafficking. Here we report protein interactions that regulate these steps. The PICK1 BAR domain interacts intermolecularly with the ABP/GRIP linker II region and intramolecularly with the PICK1 PDZ domain. Binding of PKCalpha or GluR2 to the PICK1 PDZ domain disrupts the intramolecular interaction and facilitates the PICK1 BAR domain association with ABP/GRIP. Interference with the PICK1-ABP/GRIP interaction impairs S880 phosphorylation of GluR2 by PKC and decreases the constitutive surface expression of GluR2, the NMDA-induced endocytosis of GluR2, and recycling of internalized GluR2. We suggest that the PICK1 interaction with ABP/GRIP is a critical step in controlling GluR2 trafficking.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cells, Cultured
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Cytoskeletal Proteins
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Endocytosis / drug effects
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Endocytosis / physiology
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Excitatory Amino Acid Agonists / pharmacology
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HeLa Cells
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Hippocampus / cytology
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Hippocampus / metabolism
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Humans
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Molecular Sequence Data
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N-Methylaspartate / pharmacology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Phosphorylation
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Protein Transport / physiology
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Rats
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Receptors, AMPA / metabolism*
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Tissue Distribution
Substances
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Carrier Proteins
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Cytoskeletal Proteins
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Excitatory Amino Acid Agonists
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Nerve Tissue Proteins
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Nuclear Proteins
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PICK1 protein, rat
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PICk1 protein, human
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Receptors, AMPA
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N-Methylaspartate
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glutamate receptor ionotropic, AMPA 2