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- Title
Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling.
- Authors
Nobuharu Suzuki; Tadahiro Numakawa; Chou, Joshua; de Vega, Susana; Chihiro Mizuniwa; Kaori Sekimoto; Naoki Adachi; Hiroshi Kunugi; Eri Arikawa-Hirasawa; Yoshihiko Yamada; Chihiro Akazawa
- 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. Ten4 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.
- Subjects
MEMBRANE proteins; CENTRAL nervous system; NEURONS; NEUROBLASTOMA; FILOPODIA
- Publication
FASEB Journal, 2014, Vol 28, Issue 3, p1386
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.13-241034