• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Japan - Australia Collaborative Symposium:How can animal models inform us about human brain disease

開催日 2014/9/13
時間 15:00 - 17:00
会場 Room C(502)
Chairperson(s) Seong-Seng Tan / Seong-Seng Tan (Florey Institute of Neuroscience, University of Melbourne, Australia / Florey Institute of Neuroscience, University of Melbourne, Australia)
大隅 典子 / Noriko Osumi (東北大学大学院医学系研究科 / Department of Developmental Neuroscience, Center for Neuroscience, Tohoku University Graduate School of Medicine, Japan)

A Transmembrane Protein Teneurin-4 Positively Regulates Neural and Glial Protrusion Formation through Focal Adhesion Kinase Signaling

  • S3-C-2-3
  • 赤澤 智宏 / Chihiro Akazawa:1 鈴木 喜晴 / Nobuharu Suzuki:1 馬渕 洋 / Yo Mabuchi: 
  • 1:東京医科歯科大学大学院 / Dept. Biophysics and Biochem, Graduate School of Health Sciences, Tokyo Medical and Dental University, Japan 

We recently reported that the absence of the transmembrane protein teneurin-4 (Ten-4) caused severe tremors in mice, due to hypomyelination of small diameter axons in the CNS. In this study, we characterize Ten-4 as a novel regulator of cell process formation in neural and glial cells. The length and branches of cell processes were significantly reduced in primary oligodendrocytes from Ten-4-deficient mice and in the oligodendrocyte precursor cell line CG-4, which was transfected with shRNA for Ten-4, compared with the controls. Since the oligodendrocyte-specific ablation of focal adhesion kinase (FAK) results in CNS hypomyelination of small diameter axons, we analyzed the relation of Ten-4 with FAK. The phosphorylation level of FAK in Ten-4 knockdown CG-4 cells was decreased, and a transfection of the constitutively active FAK restored the phenotype by knocking down of Ten-4 in CG-4 cells. Ten-4 is also expressed in neural cells during their neurite outgrowth. We therefore examined the molecular function of Ten-4 in neurite outgrowth of the neuroblastoma cell line Neuro-2a. Ten-4 expression was induced and Ten-4 protein was localized at the neurite growth cones. Knocking down Ten-4 expression decreased the formation of the filopodia-like cell protrusions and the length of individual neurites. Overexpression of Ten-4 conversely increased filopodia-like protrusion formation. Moreover, knockdown and overexpression of Ten-4 attenuated and promoted the activation of FAK and Rho-family small GTPases, Cdc42 and Rac1, key molecules for the protrusion formation downstream of FAK, respectively. Prevention of the activation of FAK and neural Wiskott-Aldrich syndrome protein (N-WASP), which is a downstream regulator of FAK and Cdc42, reduced the protrusion formation by Ten-4 overexpression. Further, Ten-4 was co-localized with phosphorylated FAK in the filopodia-like protrusions. Together, our findings reveal that Ten-4 is a novel positive regulator of cellular protrusion formation through FAK signaling in neural and oligodendroglial cells.

Copyright © Neuroscience2014. All Right Reserved.