Teneurin‐4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling
Teneurin‐4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling
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DOI：
10.1096/fj.13-241034
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发表时间：
2014-03
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通讯作者：
N. Suzuki;T. Numakawa;Joshua Chou;S. Vega;Chihiro Mizuniwa;K. Sekimoto;N. Adachi;H. Kunugi;E. Arikawa-Hirasawa;Yoshihiko Yamada;C. Akazawa
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作者：
N. Suzuki;T. Numakawa;Joshua Chou;S. Vega;Chihiro Mizuniwa;K. Sekimoto;N. Adachi;H. Kunugi;E. Arikawa-Hirasawa;Yoshihiko Yamada;C. Akazawa
Teneurin-4 (Ten-4) 是一种跨膜蛋白，在中枢神经系统中高表达；然而，其在神经元分化中的细胞和分子功能仍然未知。在这项研究中，我们旨在阐明 Ten-4 在神经突生长中的功能。 Ten-4 的表达在神经母细胞瘤细胞系 Neuro-2a 的神经突生长过程中被诱导。 Ten-4 蛋白定位于神经突生长锥。 Neuro-2a 细胞中 Ten-4 表达的敲低减少了丝状伪足样突起的形成和单个神经突的长度。相反，Ten-4 的过度表达促进丝状伪足样突起的形成。此外，Ten-4的敲低和过度表达分别降低和升高了粘着斑激酶（FAK）和Rho家族小GTP酶、Cdc42和Rac1的激活，它们分别是FAK下游膜突起形成的关键分子。抑制 FAK 和神经 Wiskott-Aldrich 综合征蛋白 (N-WASP)（FAK 和 Cdc42 的下游调节因子）的激活，通过 Ten-4 过表达阻止突起形成。此外，Ten-4 与磷酸化 FAK 共定位于丝状伪足状突起区域。总之，我们的研究结果表明，Ten-4 是通过 FAK 信号通路调节细胞突起形成和神经突生长的新型正调节因子。—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 通过粘着斑激酶信号传导促进细胞突起形成和神经突生长。 FASEB J. 28, 1386–1397 (2014)。 www.fasebj.org
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