PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression

Anggono, Victor, Koc-Schmitz, Yeliz, Widagdo, Jocelyn, Kormann, Jan, Quan, Annie, Chen, Chih-Ming, Robinson, Phillip J., Choi, Se-Young, Linden, David J., Plomann, Markus and Huganir, Richard L. (2013) PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the United States of America, 110 34: 13976-13981. doi:10.1073/pnas.1312467110


Author Anggono, Victor
Koc-Schmitz, Yeliz
Widagdo, Jocelyn
Kormann, Jan
Quan, Annie
Chen, Chih-Ming
Robinson, Phillip J.
Choi, Se-Young
Linden, David J.
Plomann, Markus
Huganir, Richard L.
Title PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1073/pnas.1312467110
Open Access Status DOI
Volume 110
Issue 34
Start page 13976
End page 13981
Total pages 6
Place of publication Washington, DC United States
Publisher National Academy of Sciences
Language eng
Formatted abstract
The dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses is crucial for synaptic transmission, plasticity, learning, and memory. The protein interacting with C-kinase 1 (PICK1) directly interacts with GluA2/3 subunits of the AMPARs. Although the role of PICK1 in regulating AMPAR trafficking and multiple forms of synaptic plasticity is known, the exact molecular mechanisms underlying this process remain unclear. Here, we report a unique interaction between PICK1 and all three members of the protein kinase C and casein kinase II substrate in neurons (PACSIN) family and show that they form a complex with AMPARs. Our results reveal that knockdown of the neuronal-specific protein, PACSIN1, leads to a significant reduction in AMPAR internalization following the activation of NMDA receptors in hippocampal neurons. The interaction between PICK1 and PACSIN1 is regulated by PACSIN1 phosphorylation within the variable region and is required for AMPAR endocytosis. Similarly, the binding of PICK1 to the ubiquitously expressed PACSIN2 is also regulated by the homologous phosphorylation sites within the PACSIN2-variable region. Genetic deletion of PACSIN2, which is highly expressed in Purkinje cells, eliminates cerebellar long-term depression. This deficit can be fully rescued by overexpressing wild-type PACSIN2, but not by a PACSIN2 phosphomimetic mutant, which does not bind PICK1 efficiently. Taken together, our data demonstrate that the interaction of PICK1 and PACSIN is required for the activity-dependent internalization of AMPARs and for the expression of long-term depression in the cerebellum.
Keyword Syndapin
Receptor trafficking
Synaptic Vesicle Endocytosis
Protein-Kinase-C
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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