title: Ninjurin1 enhances the basal motility and transendothelial migration of immune cells by inducing protrusive membrane dynamics.
abstract: Ninjurin1 is involved in the pathogenesis of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, by mediating leukocyte extravasation, a process that depends on homotypic binding. However, the precise regulatory mechanisms of Ninjurin1 during inflammation are largely undefined. We therefore examined the pro-migratory function of Ninjurin1 and its regulatory mechanisms in macrophages. Interestingly, Ninjurin1-deficient bone marrow-derived macrophages exhibited reduced membrane protrusion formation and dynamics, resulting in the impairment of cell motility. Furthermore, exogenous Ninjurin1 was distributed at the membrane of filopodial structures in Raw264.7 macrophage cells. In Raw264.7 cells, RNA interference of Ninjurin1 reduced the number of filopodial projections, whereas overexpression of Ninjurin1 facilitated their formation and thus promoted cell motility. Ninjurin1-induced filopodial protrusion formation required the activation of Rac1. In Raw264.7 cells penetrating an MBEC4 endothelial cell monolayer, Ninjurin1 was localized to the membrane of protrusions and promoted their formation, suggesting that Ninjurin1-induced protrusive activity contributed to transendothelial migration. Taking these data together, we conclude that Ninjurin1 enhances macrophage motility and consequent extravasation of immune cells through the regulation of protrusive membrane dynamics. We expect these findings to provide insight into the understanding of immune responses mediated by Ninjurin1.
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Bum Ju
authors.initials: BJ
authors.lastname: Ahn
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hoang
authors.initials: H
authors.lastname: Le
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Min Wook
authors.initials: MW
authors.lastname: Shin
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Bae
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Sung Yi
authors.initials: SY
authors.lastname: Lee
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Yang
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Wee
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Cha
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Seo
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hye Shin
authors.initials: HS
authors.lastname: Lee
authors.affiliation: the College of Pharmacy, Inje University, Gimhae 621-749, Korea.
authors.forename: Hyo-Jong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: the Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.affiliation: the Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: the Department of Life Science and GT5 Program, Ewha Womans University, Seodaemoon-gu, Seoul 120-750, Korea, and.
authors.forename: Sejin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: the Department of Life Science and GT5 Program, Ewha Womans University, Seodaemoon-gu, Seoul 120-750, Korea, and.
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.affiliation: the National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 402-751, Korea.
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: the National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 402-751, Korea.
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.affiliation: the National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 402-751, Korea.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
authors.affiliation: From the SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea, the Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul 151-742, Korea, qwonkim@snu.ac.kr.
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology; D034622:RNA Interference; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; D009479:Neuropeptides; C484439:Ninj1 protein, mouse; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Cell Migration; Cell Motility; Filopodia; Inflammation; Macrophage; Ninjurin1; Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); Transendothelial Migration