Repulsive migration of Schwann cells induced by Slit-2 through Ca2+-dependent RhoA-myosin signaling.
Schwann cells migrate along axons before initiating myelination during development and their migration facilitates peripheral nerve regeneration after injury. Axon guidance molecule Slit-2 is highly expressed during peripheral development and nerve regeneration; however, whether Slit-2 regulates the migration of Schwann cells remains a mystery. Here we show that Slit-2 receptor Robo-1 and Robo-2 were highly expressed in Schwann cells in vitro and in vivo. Using three distinct migration assays, we found that Slit-2 repelled the migration of cultured Schwann cells. Furthermore, frontal application of a Slit-2 gradient to migrating Schwann cells first caused the collapse of leading front, and then reversed soma translocation of Schwann cells. The repulsive effects of Slit-2 on Schwann cell migration depended on a Ca(2+) signaling release from internal stores. Interestingly, in response to Slit-2 stimulation, the collapse of leading front required the loss of F-actin and focal adhesion, whereas the subsequent reversal of soma translocation depended on RhoA-Rock-Myosin signaling pathways. Taken together, we demonstrate that Slit-2 repels the migration of cultured Schwann cells through RhoA-Myosin signaling pathways in a Ca(2+)-dependent manner.
Department of Clinical Laboratory Medicine, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Wenzhou, Zhejiang, 325035, China.
Ying
Y
Wang
Hong-Lin
HL
Teng
Zhi-Hui
ZH
Huang
D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000502:physiology*; D002464:Cell Migration Inhibition / Q000502:physiology*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009218:Myosins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*; D000098552:Slit Homolog 2 Protein
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009218:Myosins; D020742:rhoA GTP-Binding Protein; D000098552:Slit Homolog 2 Protein