title: Paxillin is the target of c-Jun N-terminal kinase in Schwann cells and regulates migration.
abstract: During development of the peripheral nervous system (PNS), Schwann cells migrate along axons, wrapping individual axons to form a myelin sheath. This process is all mediated by the intercellular signaling between neurons and Schwann cells. As yet, little is known about the intracellular signaling mechanisms controlling these morphological changes including Schwann cell migration. We previously showed that c-Jun N-terminal kinase (JNK) plays a key role in Schwann cell migration before the initiation of myelination. Here we show that JNK, acting through phosphorylation of the cytoskeletal protein paxillin, regulates Schwann cell migration and that it mediates dorsal root ganglion (DRG) neuronal conditioned medium (CM). Phosphorylation of paxillin at the Ser-178 position, the JNK phosphorylation site, is observed following stimulation with neuronal CM. Phosphorylation is also detected as a result of stimulation with each of growth factors contained in neuronal CM. Knockdown of paxillin with the specific small interfering RNA (siRNA) inhibits migration. The reintroduction of paxillin reverses siRNA-mediated inhibition of migration, whereas paxillin harboring the Ser-178-to-Ala mutation fails to reverse it. In addition, while JNK binds to the N-terminal region (called LD1), the deletion of LD1 blocks migration. Together, JNK binds and phosphorylates paxillin to regulate Schwann cell migration, illustrating that paxillin provides one of the convergent points of intracellular signaling pathways controlling Schwann cell migration.
authors: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Miyamoto
authors: Tomohiro
authors: T
authors: Torii
authors: Natsuki
authors: N
authors: Yamamori
authors: Takahiro
authors: T
authors: Eguchi
authors: Motoshi
authors: M
authors: Nagao
authors: Kazuaki
authors: K
authors: Nakamura
authors: Akito
authors: A
authors: Tanoue
authors: Junji
authors: J
authors: Yamauchi
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051419:Paxillin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051419:Paxillin; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases