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MBC in Press, published online ahead of print November 28, 2007
Mol. Biol. Cell 10.1091/mbc.E06-01-0088

A more recent version of this article appeared on February 1, 2008
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Submitted on January 30, 2006
Revised on November 5, 2007
Accepted on November 19, 2007

Paxillin Phosphorylation Controls Invadopodia/Podosomes Spatiotemporal Organization

Cédric Badowski,*{dagger} Géraldine Pawlak,*{dagger} Alexei Grichine,{dagger}{ddagger} Anne Chabadel,{sect} Christiane Oddou,*{dagger} Pierre Jurdic,{sect} Martin Pfaff,*{dagger} Corinne Albigès-Rizo,*{dagger} and Marc R. Block*{dagger}

*Equipe DySAD, Institut Albert Bonniot, INSERM U823, 38042 Grenoble Cedex 09, France; {dagger}Université Joseph Fourier, 38041 Grenoble Cedex 09, France; {ddagger}Cell Imaging Platform, Institut Albert Bonniot, INSERM U823, 38706 La Tronche Cedex, France; {sect}Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France

Monitoring Editor: Mark Ginsberg

In RSV-transformed 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 while 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. Similar mechanism is unraveled in osteoclasts using paxillin knockdown. Lack of paxillin phosphorylation, calpain or Erk inhibition, result 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 transmigration through a cell monolayer.

Address correspondence to: Marc R. Block (marc.block{at}ujf-grenoble.fr)






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