title: Interaction of the cell adhesion molecule CHL1 with vitronectin, integrins, and the plasminogen activator inhibitor-2 promotes CHL1-induced neurite outgrowth and neuronal migration.
abstract: The cell adhesion molecule close homolog of L1 (CHL1) plays important functional roles in the developing and adult nervous system. In search of the binding partners that mediate the diverse and sometimes opposing functions of CHL1, the extracellular matrix-associated proteins vitronectin and plasminogen activator inhibitor-2 (PAI-2) were identified as novel CHL1 interaction partners and tested for involvement in CHL1-dependent functions during mouse cerebellar development. CHL1-induced cerebellar neurite outgrowth and cell migration at postnatal days 6-8 were inhibited by a CHL1-derived peptide comprising the integrin binding RGD motif, and by antibodies against vitronectin or several integrins, indicating a vitronectin-dependent integrin-mediated pathway. A PAI-2-derived peptide, or antibodies against PAI-2, urokinase type plasminogen activator (uPA), uPA receptor, and several integrins reduced cell migration. CHL1 colocalized with vitronectin, PAI-2, and several integrins in cerebellar granule cells, suggesting an association among these proteins. Interestingly, at the slightly earlier age of 4-5 d, cerebellar neurons did not depend on CHL1 for neuritogenesis and cell migration. However, differentiation of progenitor cells into neurons at this stage was dependent on homophilic CHL1-CHL1 interactions. These observations indicate that homophilic CHL1 trans-interactions regulate differentiation of neuronal progenitor cells at early postnatal stages, while heterophilic trans-interactions of CHL1 with vitronectin, integrins, and the plasminogen activator system regulate neuritogenesis and neuronal cell migration at a later postnatal stage of cerebellar morphogenesis. Thus, within very narrow time windows in postnatal cerebellar development, distinct types of molecular interactions mediated by CHL1 underlie the diverse functions of this protein.
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Jelena
authors.initials: J
authors.lastname: Katic
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Loers
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kleene
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Karl
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Buck
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, BMRII-304, Birmingham, Alabama 35294.
authors.forename: Jaroslaw W
authors.initials: JW
authors.lastname: Zmijewski
authors.affiliation: Zentrum für Molekulare Neurobiologie, and.
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.affiliation: Department of Biochemistry, Medical School, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854, Center for Neuroscience, Shantou University Medical College, Shantou 515041, People's Republic of China, and schachner@biology.rutgers.edu.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse; D016023:Integrins; D017396:Plasminogen Activator Inhibitor 2; D019096:Vitronectin
keywords: CHL1; cerebellar development; integrins; migration; plasminogen system; vitronectin