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Teneurin‐4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling
Author(s) -
Suzuki Nobuharu,
Numakawa Tadahiro,
Chou Joshua,
Vega Susana,
Mizuniwa Chihiro,
Sekimoto Kaori,
Adachi Naoki,
Kunugi Hiroshi,
ArikawaHirasawa Eri,
Yamada Yoshihiko,
Akazawa Chihiro
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-241034
Subject(s) - filopodia , neurite , cdc42 , focal adhesion , microbiology and biotechnology , growth cone , gene knockdown , rac1 , biology , signal transduction , cell adhesion , adhesion , chemistry , actin , cell culture , axon , in vitro , biochemistry , genetics , organic chemistry
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.—Suzuki, N., Numakawa, T., Chou, J., de Vega, S., Mizuniwa, C., Sekimoto, K., Adachi, N., Kunugi, H., Arikawa‐Hirasawa, E., Yamada, Y., Akazawa, C. Teneurin‐4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling. FASEB J. 28, 1386–1397 (2014). www.fasebj.org