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The Journal of Neuroscience, August 1, 2001, 21(15):5417-5428
PICK1 Targets Activated Protein Kinase C to AMPA Receptor
Clusters in Spines of Hippocampal Neurons and Reduces Surface Levels of
the AMPA-Type Glutamate Receptor Subunit 2
Jose L.
Perez,
Latika
Khatri,
Craig
Chang,
Sapna
Srivastava,
Pavel
Osten, and
Edward B.
Ziff
Howard Hughes Medical Institute, Department of Biochemistry, New
York University School of Medicine, New York, New York
10016
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 C (PKC) and that the
interaction is highly dependent on the activation of the kinase. The
formation of PICK1-PKC complexes is strongly induced by TPA, and
PICK1-PKC 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 PKC 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.
Key words:
GluR2; PKC; PICK1; PDZ domain; spine; endocytosis
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155417-12$05.00/0
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