title: Cytoskeleton plays a dual role of activation and inhibition in myelin and zymosan phagocytosis by microglia.
abstract: A major innate immune function of microglia in the central nervous system is receptor-mediated phagocytosis of tissue debris and pathogens. We studied how phagocytosis of degenerated myelin (i.e., tissue debris) and zymosan (i.e., yeast pathogen) is regulated by the cytoskeleton through myosin light chain kinase (MLCK) and the small GTPase Rho and its effector Rho-kinase (ROCK) in primary mouse microglia. Our observations suggest a dual role of activation and inhibition of phagocytosis by MLCK and Rho/ROCK signaling. MLCK activated, whereas Rho/ROCK down-regulated complement receptor-3 (CR3) mediated, phagocytosis of C3bi-opsonized and nonopsonized myelin. These opposing roles of MLCK and Rho/ROCK depended on the preferential spatial localization of their distinctive functions. MLCK further activated, and Rho/ROCK down-regulated, phagocytosis of nonopsonized zymosan by nonopsonic receptors (e.g., Dectin-1). In contrast, MLCK down-regulated, but Rho/ROCK activated, CR3-mediated phagocytosis of C3bi-opsonized zymosan. Thus MLCK and Rho/ROCK can each activate or inhibit phagocytosis but always act in opposition. Whether activation or inhibition occurs depends on the nature of the phagocytosed particle (C3bi-opsonized or nonopsonized myelin or zymosan) and the receptors mediating each phagocytosis.
authors.affiliation: Department of Medical Neurobiology, Hebrew University-Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Gitik
authors.forename: Fanny
authors.initials: F
authors.lastname: Reichert
authors.forename: Shlomo
authors.initials: S
authors.lastname: Rotshenker
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D007113:Immunity, Innate; D051379:Mice; D017628:Microglia / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D009219:Myosin-Light-Chain Kinase / Q000276:immunology; D010587:Phagocytosis; D015054:Zymosan / Q000276:immunology*; D020741:rho GTP-Binding Proteins / Q000276:immunology; D054460:rho-Associated Kinases / Q000276:immunology
chemical_list: D015054:Zymosan; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D020741:rho GTP-Binding Proteins