Fujita Toshitsugu, Maturana Andrés D, Ikuta Junko, Hamada Juri, Walchli Sebastien, Suzuki Tadaki, Sawa Hirofumi, Wooten Marie W, Okajima Toshihide, Tatematsu Kenji, Tanizawa Katsuyuki, Kuroda Shun'ichi
Department of Structural Molecular Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
Biochem Biophys Res Commun. 2007 Sep 28;361(3):605-10. doi: 10.1016/j.bbrc.2007.07.050. Epub 2007 Jul 23.
Fasciculation and elongation protein zeta-1 (FEZ1) promotes efficiently the neurite elongation of rat phaeochromocytoma PC12 cells. We here characterized FEZ1 in PC12 cells. Nerve growth factor (NGF) stimulation induces significant expression of endogenous FEZ1 in PC12 cells. Upon NGF stimulation FEZ1 localizes in both cytoplasm and neuritis, co-localizing with mitochondria. Silencing of FEZ1 by RNA interference efficiently reduces NGF-induced neurite elongation and the anterograde motility of mitochondria in PC12 cells. Immunoprecipitation and pulldown assay shows that FEZ1 interacts with kinesin superfamily protein 5 (KIF5) and tubulin. Thus, our results suggest that the FEZ1/kinesin complex functions for the transport of mitochondria along microtubules toward the extending neurites in differentiating PC12 cells.
成束和延伸蛋白ζ-1（FEZ1）可有效促进大鼠嗜铬细胞瘤PC12细胞的神经突延伸。我们在此对PC12细胞中的FEZ1进行了表征。神经生长因子（NGF）刺激可诱导PC12细胞中内源性FEZ1的显著表达。在NGF刺激下，FEZ1定位于细胞质和神经突中，与线粒体共定位。通过RNA干扰使FEZ1沉默可有效降低PC12细胞中NGF诱导的神经突延伸和线粒体的顺向运动。免疫沉淀和下拉试验表明，FEZ1与驱动蛋白超家族蛋白5（KIF5）和微管蛋白相互作用。因此，我们的结果表明，FEZ1/驱动蛋白复合物在分化的PC12细胞中发挥作用，使线粒体沿着微管向延伸的神经突运输。
