title: Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling.
abstract: Teneurin-4 (Ten-4), a transmembrane protein, is highly expressed in the central nervous system; however, its cellular and molecular function in neuronal differentiation remains unknown. In this study, we aimed to elucidate the function of Ten-4 in neurite outgrowth. Ten-4 expression was induced during neurite outgrowth of the neuroblastoma cell line Neuro-2a. Ten-4 protein was localized at the neurite growth cones. Knockdown of Ten-4 expression in Neuro-2a cells decreased the formation of the filopodia-like protrusions and the length of individual neurites. Conversely, overexpression of Ten-4 promoted filopodia-like protrusion formation. In addition, knockdown and overexpression of Ten-4 reduced and elevated the activation of focal adhesion kinase (FAK) and Rho-family small GTPases, Cdc42 and Rac1, key molecules for the membranous protrusion formation downstream of FAK, respectively. Inhibition of the activation of FAK and neural Wiskott-Aldrich syndrome protein (N-WASP), which is a downstream regulator of FAK and Cdc42, blocked protrusion formation by Ten-4 overexpression. Further, Ten-4 colocalized with phosphorylated FAK in the filopodia-like protrusion regions. Together, our findings show that Ten-4 is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the FAK signaling pathway.
authors.affiliation: 1Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bldg 3, Bunkyo-ku, Tokyo, Japan, 113-8510. c.akazawa.bb@tmd.ac.jp.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Joshua
authors.initials: J
authors.lastname: Chou
authors.forename: Susana
authors.initials: S
authors.lastname: de Vega
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mizuniwa
authors.forename: Kaori
authors.initials: K
authors.lastname: Sekimoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Eri
authors.initials: E
authors.lastname: Arikawa-Hirasawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akazawa
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D016501:Neurites; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C113761:Tenm4 protein, mouse; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: cytoskeleton; neuronal differentiation