title: Collagen remodeling by phagocytosis is determined by collagen substrate topology and calcium-dependent interactions of gelsolin with nonmuscle myosin IIA in cell adhesions.
abstract: We examine how collagen substrate topography, free intracellular calcium ion concentration ([Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]i, time- and Ca(2+)-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, Ca(2+)-dependent binding to full-length NMMIIA. Gelsolin domains G4-G6 selectively require Ca(2+) to interact with NMMIIA, which is restricted to residues 1339-1899 of NMMIIA. We conclude that cell adhesion to collagen presented on beads activates Ca(2+) entry and promotes the formation of phagosomes enriched with NMMIIA and gelsolin. The Ca(2+) -dependent interaction of gelsolin and NMMIIA in turn enables actin remodeling and enhances collagen degradation by phagocytosis.
authors: Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors: P D
authors: PD
authors: Arora
authors: Y
authors: Y
authors: Wang
authors: A
authors: A
authors: Bresnick
authors: J
authors: J
authors: Dawson
authors: P A
authors: PA
authors: Janmey
authors: C A
authors: CA
authors: McCulloch
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts; D022001:Focal Adhesions; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000199:Actins; D018260:Gelsolin; D034741:RNA, Small Interfering; D003094:Collagen; D024507:Nonmuscle Myosin Type IIA; D002118:Calcium