Shirane Michiko, Nakayama Keiichi I
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Science. 2006 Nov 3;314(5800):818-21. doi: 10.1126/science.1134027.
Guanosine triphosphatases of the Rab family are key regulators of membrane trafficking, with Rab11 playing a specific role in membrane recycling. We identified a mammalian protein, protrudin, that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11. Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK) in response to nerve growth factor promoted protrudin association with Rab11-GDP. Down-regulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus, protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation.
Rab 家族的鸟苷三磷酸酶是膜运输的关键调节因子,其中 Rab11 在膜回收中发挥特定作用。我们鉴定出一种哺乳动物蛋白——突出蛋白,它通过与鸟苷二磷酸(GDP)结合形式的 Rab11 相互作用来促进神经突形成。细胞外信号调节激酶(ERK)响应神经生长因子对突出蛋白的磷酸化促进了突出蛋白与 Rab11-GDP 的结合。通过 RNA 干扰下调突出蛋白会导致膜向各个方向延伸并抑制神经突形成。因此,突出蛋白调节 Rab11 依赖的膜回收,以促进神经突形成所需的定向膜运输。