title: UDP-Induced Phagocytosis and ATP-Stimulated Chemotactic Migration Are Impaired inSTIM1-/-Microglia In Vitro and In Vivo.
abstract: STIM1 is the only currently known intracellular calcium sensor that functions as the calcium influx regulator controlling immune cell activation. STIM1 function in immune cell calcium signalling has been studied extensively; however, its role in microglia, innate immune cells in brain, has not been fully understood. Here, we report thatSTIM1-/-murine microglia lost store-operated calcium influx and displayed aberrant immunological functions. Microglial functions regulated by chronic and global [Ca2+]ichanges were reduced significantly, including cytokine releases and opsonin-dependent phagocytosis. More dramatically, cellular functions governed by Ca2+regulation in local microdomains at the cell periphery, such as UDP-induced phagocytosis and ATP-stimulated chemotactic migration, were severely reduced inSTIM1-/-microglia. Interestingly, UDP-induced Orai1 mobilization to the peripheral region was greatly attenuated inSTIM1-/-microglia. Their chemotactic migration defect was reproduced in vivo in embryonic brain; the aggregated number ofSTIM1-/-microglia in LPS- (lipopolysaccharide-) injected lesions was much smaller than that in wild-type microglia. Furthermore, the neuron phagoptosis activities of activated microglia were significantly diminished in theSTIM1-/-microglia. These in vitro and in vivo results suggest that STIM1-mediated store-operated calcium entry is important for the regulation of global [Ca2+]ichanges which differentiates into active immune state of microglia, but it is more crucial for the regulation of local [Ca2+] microdomains which mediates the acute motility of murine microglia.
authors.affiliation: Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Lim
authors.affiliation: Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Heo
authors.initials: H
authors.lastname: Woon
authors.affiliation: Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Han
authors.affiliation: Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Joo Young
authors.identifier: 0000-0003-2623-1491
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000071740:ORAI1 Protein / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D000071737:Stromal Interaction Molecule 1 / Q000172:deficiency* / Q000235:genetics; D014530:Uridine Diphosphate / Q000378:metabolism*
chemical_list: D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D014530:Uridine Diphosphate; D000255:Adenosine Triphosphate