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J Cell Biol. 2016 Jun 6;213(5):585-99. doi: 10.1083/jcb.201510036.

Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes.

Author information

1
Institut Albert Bonniot, Institut National de la Santé et de la Recherche Médicale U823, 38042 Grenoble, France Université Grenoble Alpes, 38400 Saint-Martin-d'Hères, France Equipe de Recherche Labellisée, Centre National de la Recherche Scientifique 5284, 38042 Grenoble, France.
2
Institut Albert Bonniot, Institut National de la Santé et de la Recherche Médicale U823, 38042 Grenoble, France Université Grenoble Alpes, 38400 Saint-Martin-d'Hères, France.
3
Department of Pathology, University of Virginia, Charlottesville, VA 22908.
4
Department of Biochemistry, Showa University School of Medicine, Tokyo 142-8555, Japan.
5
Institut de Recherche en Technologies et Sciences pour le Vivant-Biologie à Grande Échelle, Université Grenoble Alpes, 38000 Grenoble, France Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Recherche en Technologies et Sciences pour le Vivant-Biologie à Grande Échelle, 38000 Grenoble, France Institut National de la Santé et de la Recherche Médicale, Laboratoire Biologie à Grande Échelle, 38000 Grenoble, France.
6
Institut Albert Bonniot, Institut National de la Santé et de la Recherche Médicale U823, 38042 Grenoble, France Université Grenoble Alpes, 38400 Saint-Martin-d'Hères, France Equipe de Recherche Labellisée, Centre National de la Recherche Scientifique 5284, 38042 Grenoble, France olivier.destaing@ujf-grenoble.fr.

Abstract

Invadosomes are acto-adhesive structures able to both bind the extracellular matrix (ECM) and digest it. Paxillin family members-paxillin, Hic-5, and leupaxin-are implicated in mechanosensing and turnover of adhesion sites, but the contribution of each paxillin family protein to invadosome activities is unclear. We use genetic approaches to show that paxillin and Hic-5 have both redundant and distinctive functions in invadosome formation. The essential function of paxillin-like activity is based on the coordinated activity of LD motifs and LIM domains, which support invadosome assembly and morphology, respectively. However, paxillin preferentially regulates invadosome assembly, whereas Hic-5 regulates the coupling between ECM degradation and acto-adhesive functions. Mass spectrometry analysis revealed new partners that are important for paxillin and Hic-5 specificities: paxillin regulates the acto-adhesive machinery through janus kinase 1 (JAK1), whereas Hic-5 controls ECM degradation via IQGAP1. Integrating the redundancy and specificities of paxillin and Hic-5 in a functional complex provides insights into the coupling between the acto-adhesive and ECM-degradative machineries in invadosomes.

PMID:
27269065
PMCID:
PMC4896053
DOI:
10.1083/jcb.201510036
[Indexed for MEDLINE]
Free PMC Article

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