Collagen remodeling by phagocytosis is determined by collagen substrate topology and calcium-dependent interactions of gelsolin with nonmuscle myosin IIA in cell adhesions

P. D. Arora, Y. Wang, Anne R. Bresnick, J. Dawson, P. A. Janmey, C. A. McCulloch

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We examine how collagen substrate topography, free intracellular calcium ion concentration ([Ca2+]i, and the association of gelsolin with nonmuscle myosin IIA (NMMIIA) at collagen adhesions are regulated to enable collagen phagocytosis. Fibroblasts plated on planar, collagen-coated substrates show minimal increase of [Ca2+]i, minimal colocalization of gelsolin and NMMIIA in focal adhesions, and minimal intracellular collagen degradation. In fibroblasts plated on collagen-coated latex beads there are large increases of [Ca2+]i, time- and Ca2+-dependent enrichment of NMMIIA and gelsolin at collagen adhesions, and abundant intracellular collagen degradation. NMMIIA knockdown retards gelsolin recruitment to adhesions and blocks collagen phagocytosis. Gelsolin exhibits tight, Ca2+-dependent binding to full-length NMMIIA. Gelsolin domains G4-G6 selectively require Ca2+ to interact with NMMIIA, which is restricted to residues 1339-1899 of NMMIIA. We conclude that cell adhesion to collagen presented on beads activates Ca2+ entry and promotes the formation of phagosomes enriched with NMMIIA and gelsolin. The Ca2+ -dependent interaction of gelsolin and NMMIIA in turn enables actin remodeling and enhances collagen degradation by phagocytosis.

Original languageEnglish (US)
Pages (from-to)734-747
Number of pages14
JournalMolecular Biology of the Cell
Volume24
Issue number6
DOIs
StatePublished - Mar 15 2013

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Nonmuscle Myosin Type IIA
Gelsolin
Phagocytosis
Cell Adhesion
Collagen
Calcium
Fibroblasts
Phagosomes
Focal Adhesions
Microspheres
Actins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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Collagen remodeling by phagocytosis is determined by collagen substrate topology and calcium-dependent interactions of gelsolin with nonmuscle myosin IIA in cell adhesions. / Arora, P. D.; Wang, Y.; Bresnick, Anne R.; Dawson, J.; Janmey, P. A.; McCulloch, C. A.

In: Molecular Biology of the Cell, Vol. 24, No. 6, 15.03.2013, p. 734-747.

Research output: Contribution to journalArticle

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