RGD Reference Report - Changes in the balance between caldesmon regulated by p21-activated kinases and the Arp2/3 complex govern podosome formation. - Rat Genome Database
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Changes in the balance between caldesmon regulated by p21-activated kinases and the Arp2/3 complex govern podosome formation.

Authors: Morita, T  Mayanagi, T  Yoshio, T  Sobue, K 
Citation: Morita T, etal., J Biol Chem. 2007 Mar 16;282(11):8454-63. Epub 2007 Jan 15.
RGD ID: 2306207
Pubmed: (View Article at PubMed) PMID:17224451
DOI: Full-text: DOI:10.1074/jbc.M609983200

Podosomes are dynamic cell adhesion structures that degrade the extracellular matrix, permitting extracellular matrix remodeling. Accumulating evidence suggests that actin and its associated proteins play a crucial role in podosome dynamics. Caldesmon is localized to the podosomes, and its expression is down-regulated in transformed and cancer cells. Here we studied the regulatory mode of caldesmon in podosome formation in Rous sarcoma virus-transformed fibroblasts. Exogenous expression analyses revealed that caldesmon represses podosome formation triggered by the N-WASP-Arp2/3 pathway. Conversely, depletion of caldesmon by RNA interference induces numerous small-sized podosomes with high dynamics. Caldesmon competes with the Arp2/3 complex for actin binding and thereby inhibits podosome formation. p21-activated kinases (PAK)1 and 2 are also repressors of podosome formation via phosphorylation of caldesmon. Consequently, phosphorylation of caldesmon by PAK1/2 enhances this regulatory mode of caldesmon. Taken together, we conclude that in Rous sarcoma virus-transformed cells, changes in the balance between PAK1/2-regulated caldesmon and the Arp2/3 complex govern the formation of podosomes.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Actr3  (actin related protein 3)
Arpc2  (actin related protein 2/3 complex, subunit 2)


Additional Information