title: Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition.
abstract: Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca(2+) release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca(2+)-dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca(2+) and cofilin signaling during Slit-2-triggered repulsion.
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhi-da
authors.initials: ZD
authors.lastname: Su
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Geng
authors.forename: Yi-Zhang
authors.initials: YZ
authors.lastname: Chen
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Yuan
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000098552:Slit Homolog 2 Protein
chemical_list: D051338:Cofilin 1; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020742:rhoA GTP-Binding Protein; D000098552:Slit Homolog 2 Protein; D002118:Calcium