Biomaterial Database

Cytoskeleton plays a dual role of activation and inhibition in myelin and zymosan phagocytosis by microglia. 2010

Miri Gitik, and Fanny Reichert, and Shlomo Rotshenker

Department of Medical Neurobiology, Hebrew University-Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.

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.

UI	MeSH Term	Description	Entries
D007113	Immunity, Innate	The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.	Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D009186	Myelin Sheath	The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.	Myelin,Myelin Sheaths,Sheath, Myelin,Sheaths, Myelin
D009219	Myosin-Light-Chain Kinase	An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.	Myosin Kinase,Myosin LCK,Myosin Regulatory Light-Chain Kinase,Kinase, Myosin,Kinase, Myosin-Light-Chain,LCK, Myosin,Myosin Light Chain Kinase,Myosin Regulatory Light Chain Kinase
D010587	Phagocytosis	The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).	Phagocytoses
D003599	Cytoskeleton	The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.	Cytoplasmic Filaments,Cytoskeletal Filaments,Microtrabecular Lattice,Cytoplasmic Filament,Cytoskeletal Filament,Cytoskeletons,Filament, Cytoplasmic,Filament, Cytoskeletal,Filaments, Cytoplasmic,Filaments, Cytoskeletal,Lattice, Microtrabecular,Lattices, Microtrabecular,Microtrabecular Lattices
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015054	Zymosan		Zymosan A
D017628	Microglia	The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.	Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054460	rho-Associated Kinases	A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.	rho-Associated Kinase,ROCK Protein Kinases,ROCK-I Protein Kinase,ROCK-II Protein Kinase,ROK Kinase,p160 rhoA-Binding Kinase ROKalpha,p160ROCK,rho-Associated Coiled-Coil Containing Protein Kinase 1,rho-Associated Coiled-Coil Containing Protein Kinase 2,rho-Associated Coiled-Coil Kinase,rho-Associated Kinase 1,rho-Associated Kinase 2,rho-Associated Kinase alpha,rho-Associated Kinase beta,rho-Associated Protein Kinase alpha,rho-Associated Protein Kinase beta,rho-Kinase,Coiled-Coil Kinase, rho-Associated,Protein Kinases, ROCK,ROCK I Protein Kinase,ROCK II Protein Kinase,p160 rhoA Binding Kinase ROKalpha,rho Associated Coiled Coil Containing Protein Kinase 1,rho Associated Coiled Coil Containing Protein Kinase 2,rho Associated Coiled Coil Kinase,rho Associated Kinase,rho Associated Kinase 1,rho Associated Kinase 2,rho Associated Kinase alpha,rho Associated Kinase beta,rho Associated Kinases,rho Associated Protein Kinase alpha,rho Associated Protein Kinase beta,rho Kinase