Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Nature cell biology | Mar 26, 2008

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.

Pubmed ID: 18297063 RIS Download

Mesh terms: Actin-Related Protein 2-3 Complex | Actins | Animals | Carrier Proteins | Cell Movement | Cytoskeleton | Endocytosis | Gene Expression Regulation | Hippocampus | Models, Biological | Neurons | Nuclear Proteins | Protein Structure, Tertiary | Rats | Rats, Wistar | Receptors, AMPA

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: Wellcome Trust, Id: 072005
  • Agency: Medical Research Council, Id: G0501455
  • Agency: Medical Research Council, Id: G0501455(76848)
  • Agency: Wellcome Trust, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.