Paxillin Phosphorylation Controls Invadopodia/Podosomes Spatiotemporal Organization Paxillin phosphorylation and invadopodia dynamics

In Rous sarcoma virus (RSV)-transformed baby hamster kidney (BHK) cells, invadopodia can self-organize into rings and belts, similarly to podosome distribution during osteoclast differentiation. The composition of individual invadopodia is spatiotemporally regulated and depends on invadopodia locali...

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Published inMolecular biology of the cell Vol. 19; no. 2; pp. 633 - 645
Main Authors Badowski, Cédric, Pawlak, Géraldine, Grichine, Alexei, Chabadel, Anne, Oddou, Christiane I., Jurdic, Pierre, Pfaff, Martin, Albiges-Rizo, Corinne, Block, Marc R.
Format Journal Article
LanguageEnglish
Published American Society for Cell Biology 01.02.2008
Subjects
Cellular Biology
Life Sciences
podosomes
paxilline
invadopodia
cell invasion
adhesion
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Summary:In Rous sarcoma virus (RSV)-transformed baby hamster kidney (BHK) cells, invadopodia can self-organize into rings and belts, similarly to podosome distribution during osteoclast differentiation. The composition of individual invadopodia is spatiotemporally regulated and depends on invadopodia localization along the ring section: the actin core assembly precedes the recruitment of surrounding integrins and integrin-linked proteins, whereas the loss of the actin core was a prerequisite to invadopodia disassembly. We have shown that invadopodia ring expansion is controlled by paxillin phosphorylations on tyrosine 31 and 118, which allows invadopodia disassembly. In BHK-RSV cells, ectopic expression of the paxillin mutant Y31F-Y118F induces a delay in invadopodia disassembly and impairs their self-organization. A similar mechanism is unraveled in osteoclasts by using paxillin knockdown. Lack of paxillin phosphorylation, calpain or extracellular signal-regulated kinase inhibition, resulted in similar phenotype, suggesting that these proteins belong to the same regulatory pathways. Indeed, we have shown that paxillin phosphorylation promotes Erk activation that in turn activates calpain. Finally, we observed that invadopodia/podosomes ring expansion is required for efficient extracellular matrix degradation both in BHK-RSV cells and primary osteoclasts, and for transmigration through a cell monolayer.
ISSN:1939-4586
DOI:10.1091/mbc.E06-01-0088