title: Protocadherin-17 mediates collective axon extension by recruiting actin regulator complexes to interaxonal contacts.
abstract: In the process of neuronal wiring, axons derived from the same functional group typically extend together, resulting in fascicle formation. How these axons communicate with one another remains largely unknown. Here, we show that protocadherin-17 (Pcdh17) supports this group extension by recruiting actin polymerization regulators to interaxonal contact sites. Pcdh17 is expressed by a subset of amygdala neurons, and it accumulates at axon-axon boundaries because of homophilic binding. Pcdh17 knockout in mice suppressed the extension of these axons. Ectopically expressed Pcdh17 altered the pattern of axon extension. In in-vitro cultures, wild-type growth cones normally migrate along other axons, whereas Pcdh17 null growth cones do not. Pcdh17 recruits the WAVE complex, Lamellipodin, and Ena/VASP to cell-cell contacts, converting these sites into motile structures. We propose that, through these mechanisms, Pcdh17 maintains the migration of growth cones that are in contact with other axons, thereby supporting their collective extension.
authors.affiliation: Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Laboratory for Electron Microscope, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Misaki
authors.affiliation: Laboratory for Integrated Biodevice, RIKEN Quantitative Biology Center, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriguchi
authors.affiliation: Laboratory for Integrated Biodevice, RIKEN Quantitative Biology Center, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Laboratory for Cell Adhesion and Tissue Patterning, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: takeichi@cdb.riken.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeichi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000679:Amygdala / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D000091363:Protocadherins; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; C504473:Pcdh1 protein, mouse; D000091363:Protocadherins; D051300:Wiskott-Aldrich Syndrome Protein Family