title: Induction of axon growth arrest without growth cone collapse through the N-terminal region of four-transmembrane glycoprotein M6a.
abstract: During development, axons elongate vigorously, carefully controlling their speed, to connect with their targets. In general, rapid axon growth is correlated with active growth cones driven by dynamic actin filaments. For example, when the actin-driven tip is collapsed by repulsive guidance molecules, axon growth is severely impaired. In this study, we report that axon growth can be suppressed, without destroying the actin-based structure or motility of the growth cones, when antibodies bind to the four-transmembrane glycoprotein M6a concentrated on the growth cone edge. Surprisingly, M6a-deficient axons grow actively but are not growth suppressed by the antibodies, arguing for an inductive action of the antibody. The binding of antibodies clusters and displaces M6a protein from the growth cone edge membrane, suggesting that the spatial rearrangement of this protein might underlie the unique growth cone behavior triggered by the antibodies. Molecular dissection of M6a suggested involvement for the N-terminal intracellular domain in this antibody-induced growth cone arrest.
authors.affiliation: Division of Brain Function, National Institute of Genetics, Yata 1111, Mishima 411-8540, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Sakura
authors.initials: S
authors.lastname: Mita
authors.forename: Nanae
authors.initials: N
authors.lastname: Fukushima
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Hirata
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived; D001369:Axons / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D020439:Growth Cones / Q000378:metabolism* / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D061251:Primary Cell Culture
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C083480:Gpm6a protein, mouse; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments