title: Regulation of Integrin α6 Recycling by Calcium-independent Phospholipase A2 (iPLA2) to Promote Microglia Chemotaxis on Laminin.
abstract: Microglia are the immune effector cells that are activated in response to pathological changes in the central nervous system. Microglial activation is accompanied by the alteration of integrin expression on the microglia surface. However, changes of integrin expression upon chemoattractant (ADP) stimulation still remain unknown. In this study, we investigated whether ADP induces the alteration of integrin species on the cell surface, leading to changes in chemotactic ability on different extracellular matrix proteins. Flow cytometry scans and on-cell Western assays showed that ADP stimulation induced a significant increase of α6 integrin-GFP, but not α5, on the surface of microglia cells. Microglia also showed a greater motility increase on laminin than fibronectin after ADP stimulation. Time lapse microscopy and integrin endocytosis assay revealed the essential role of calcium-independent phospholipase A2activity for the recycling of α6 integrin-GFP from the endosomal recycling complex to the plasma membrane. Lack of calcium-independent phospholipase A2activity caused a reduced rate of focal adhesion formation on laminin at the leading edge. Our results suggest that the alteration of integrin-mediated adhesion may regulate the extent of microglial infiltration into the site of damage by controlling their chemotactic ability.
authors.affiliation: From the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600.|Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea, and.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: From the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600.
authors.forename: Neetu
authors.initials: N
authors.lastname: Sud
authors.affiliation: From the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600.
authors.forename: Narae
authors.initials: N
authors.lastname: Lee
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Selvaraj
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: From the Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600, chang.chung@vanderbilt.edu.|School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Chang Y
authors.initials: CY
authors.lastname: Chung
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D039503:Integrin alpha6; D007797:Laminin; D034741:RNA, Small Interfering; D000244:Adenosine Diphosphate; D054512:Phospholipases A2, Calcium-Independent
keywords: chemotaxis; focal adhesion; integrin; microglia; phospholipase A