title: A collapsin response mediator protein 2 isoform controls myosin II-mediated cell migration and matrix assembly by trapping ROCK II.
abstract: Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, and Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark. ayoneda@toyaku.ac.jp
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yoneda
authors.forename: Marie
authors.initials: M
authors.lastname: Morgan-Fisher
authors.forename: Robin
authors.initials: R
authors.lastname: Wait
authors.forename: John R
authors.initials: JR
authors.lastname: Couchman
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Wewer
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D020033:Protein Isoforms / Q000378:metabolism; D012326:RNA Splicing; D051381:Rats; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C095114:collapsin response mediator protein-2; D054460:rho-Associated Kinases; D024462:Myosin Type II