RGD Reference Report - Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis. - Rat Genome Database

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Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis.

Authors: Rocca, DL  Martin, S  Jenkins, EL  Hanley, JG 
Citation: Rocca DL, etal., Nat Cell Biol. 2008 Mar;10(3):259-71. doi: 10.1038/ncb1688. Epub 2008 Feb 24.
RGD ID: 8554748
Pubmed: (View Article at PubMed) PMID:18297063
DOI: Full-text: DOI:10.1038/ncb1688

The dynamic regulation of actin polymerization plays crucial roles in cell morphology and endocytosis. The mechanistic details of these processes and the proteins involved are not fully understood, especially in neurons. PICK1 is a PDZ-BAR-domain protein involved in regulated AMPA receptor (AMPAR) endocytosis in neurons. Here, we demonstrate that PICK1 binds filamentous (F)-actin and the actin-nucleating Arp2/3 complex, and potently inhibits Arp2/3-mediated actin polymerization. RNA interference (RNAi) knockdown of PICK1 in neurons induces a reorganization of the actin cytoskeleton resulting in aberrant cell morphology. Wild-type PICK1 rescues this phenotype, but a mutant PICK1, PICK1(W413A), that does not bind or inhibit Arp2/3 has no effect. Furthermore, this mutant also blocks NMDA-induced AMPAR internalization. This study identifies PICK1 as a negative regulator of Arp2/3-mediated actin polymerization that is critical for a specific form of vesicle trafficking, and also for the development of neuronal architecture.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Arpc2  (actin related protein 2/3 complex, subunit 2)
Gria2  (glutamate ionotropic receptor AMPA type subunit 2)
Pick1  (protein interacting with PRKCA 1)


Additional Information