GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: Evidence supporting an adapter function for GLUTICBP
GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: Evidence supporting an adapter function for GLUTICBP
复制标题
DOI：
10.1091/mbc.e04-11-0978
复制
发表时间：
2005-09-01
影响因子：
3.3
通讯作者：
Bunn, RC
中科院分区：
文献类型：
--
作者：
Reed, BC;Cefalu, C;Bunn, RC
我们确定了一种新的肌球蛋白VI和GLUT 1转运蛋白结合蛋白GLUT 1CBP（GIPC 1）之间的相互作用，并首次提出，作为一个适配器分子，它可能起到耦合囊泡结合蛋白肌球蛋白VI运动。本研究通过鉴定GIPC 1 C末端中的两个肌球蛋白VI结合结构域，将各自的寡聚化和肌球蛋白VI结合功能分配到单独的N-和C-末端结构域，并定义结合GIPC 1的肌球蛋白VI尾中的中心区域来改进模型。进一步支持该模型的数据表明：1）肌球蛋白VI和GIPC 1的相互作用不需要介导蛋白; 2）GIPC 1中的肌球蛋白VI结合结构域对于GIPC 1与肌球蛋白VI的细胞内相互作用以及过表达的肌球蛋白VI向膜结构的募集是必需的，但对于GIPC 1与这些结构的缔合不是必需的; 3）GIPC 1/肌球蛋白VI复合物以肌动蛋白依赖性和微管非依赖性的方式在细胞的细胞延伸内协调运动;和4）阻断GIPC 1与肌球蛋白VI的相互作用或GLUT 1与GIPC 1的相互作用破坏极化上皮细胞中的正常GLUT 1运输，导致质膜中GLUT 1水平的降低和伴随的内膜结构中的积累。
We identified a novel interaction between myosin VI and the GLUT1 transporter binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it might function to couple vesicle-bound proteins to myosin VI movement. This study refines the model by identifying two myosin VI binding domains in the GIPC1 C terminus, assigning respective oligomerization and myosin VI binding functions to separate N- and C-terminal domains, and defining a central region in the myosin VI tail that binds GIPC1. Data further supporting the model demonstrate that 1) myosin VI and GIPC1 interactions do not require a mediating protein; 2) the myosin VI binding domain in GIPC1 is necessary for intracellular interactions of GIPC1 with myosin VI and recruitment of overexpressed myosin VI to membrane structures, but not for the association of GIPC1 with such structures; 3) GIPC1/myosin VI complexes coordinately move within cellular extensions of the cell in an actin-dependent and microtubule-independent manner; and 4) blocking either GIPC1 interactions with myosin VI or GLUT1 interactions with GIPC1 disrupts normal GLUT1 trafficking in polarized epithelial cells, leading to a reduction in the level of GLUT1 in the plasma membrane and concomitant accumulation in internal membrane structures.