C. elegans PAT-6/actopaxin plays a critical role in the assembly of integrin adhesion complexes in vivo

Xinyi Lin, Hiroshi Qadota, Donald G. Moerman, Benjamin D. Williams

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The novel focal adhesion protein actopaxin includes tandem unconventional calponin homology (CH) domains and a less well-conserved N-terminal stretch. Dominant-negative studies have implicated actopaxin in focal adhesion formation. Results: PAT-6/actopaxin, the sole actopaxin homolog in C. elegans, is located in body wall muscle attachments that are in vivo homologs of focal adhesions. We show using pat-6 protein null alleles that PAT-6/actopaxin has critical nonredundant roles during attachment maturation. It is required to recruit UNC-89 and myofilaments to newly forming attachments, and also to reposition the attachments so that they form the highly ordered array of dense body and M line attachments that are characteristic of mature muscle cells. PAT-6/actopaxin is not required for the deposition of UNC-52/perlecan in the basal lamina, nor for the initiation of attachment assembly, including the clustering of integrin into foci and the recruitment of attachment proteins PAT-4/ILK, UNC-112, and DEB-1/vinculin from the cytosol. PAT-6/actopaxin, PAT-4/ILK, and UNC-112 are each required for the same steps during attachment assembly in vivo, consistent with the notion that they work together in multiprotein complex. Supporting this idea, PAT-4/ILK can simultaneously bind to PAT-6/actopaxin and UNC-112, forming a ternary complex, in yeast three-hybrid assays. Finally, we show that both calponin homology domains are required for PAT-6/actopaxin's critical functions during attachment assembly in vivo. Conclusions: We show directly by loss-of-function genetics that PAT-6/actopaxin plays essential roles during the maturation of integrin-mediated muscle attachments in vivo.

Original languageEnglish (US)
Pages (from-to)922-932
Number of pages11
JournalCurrent Biology
Volume13
Issue number11
DOIs
StatePublished - May 27 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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