Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein.

Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein.
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DOI:
10.1083/jcb.115.6.1639
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发表时间:
1991-12
影响因子:
7.8
通讯作者:
Cleveland, D W
Cleveland, D W
中科院分区:
生物学1区
文献类型:
--
作者:
Gill, S R;Schroer, T A;Szilak, I;Steuer, E R;Sheetz, M P;Cleveland, D W

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虽然细胞质动力蛋白是已知的微管和易位向其负端,动力蛋白的能力,在体外作为一个负端定向转运膜细胞器依赖于其他可溶性因子。我们在此表明,大约20 S的多肽复合物(称为激活剂I; Schroer,T.一、和M. P. Sheetz 1991年a。115:1309-1318)。刺激动力蛋白介导的囊泡运输。激活剂复合物的一个主要组成部分是一个150 kD的多肽的双峰,我们建议的名称dynactin(动力蛋白激活剂)。20 S dynactin复合物是体外囊泡运动所需的,因为用针对dynactin的mAb耗尽它消除了囊泡运动。从鸡中克隆出一种脑特异性的动力肌动蛋白亚型,揭示了一种由1,053个氨基酸组成的多肽,它由两个卷曲螺旋α-螺旋结构域组成,中间被间隔区打断。这种结构基序和基础的一级序列在脊椎动物中高度保守,在鸡和大鼠蛋白质的中央1,000个残基结构域内具有85%的序列同一性。与动力蛋白一样丰富,动力蛋白是普遍表达的,似乎由一个单一的基因编码,产生至少三种可供选择的同种型。果蝇中可能的同源物是Glued基因,其蛋白质产物与脊椎动物动力蛋白有50%的序列同一性,其功能对生物体中大多数(也许是所有)细胞的生存能力至关重要。
Although cytoplasmic dynein is known to attach to microtubules and translocate toward their minus ends, dynein's ability to serve in vitro as a minus end-directed transporter of membranous organelles depends on additional soluble factors. We show here that a approximately 20S polypeptide complex (referred to as Activator I; Schroer, T. A., and M.P. Sheetz. 1991a. J. Cell Biol. 115:1309-1318.) stimulates dynein- mediated vesicle transport. A major component of the activator complex is a doublet of 150-kD polypeptides for which we propose the name dynactin (for dynein activator). The 20S dynactin complex is required for in vitro vesicle motility since depletion of it with a mAb to dynactin eliminates vesicle movement. Cloning of a brain specific isoform of dynactin from chicken reveals a 1,053 amino acid polypeptide composed of two coiled-coil alpha-helical domains interrupted by a spacer. Both this structural motif and the underlying primary sequence are highly conserved in vertebrates with 85% sequence identity within a central 1,000-residue domain of the chicken and rat proteins. As abundant as dynein, dynactin is ubiquitously expressed and appears to be encoded by a single gene that yields at least three alternative isoforms. The probable homologue in Drosophila is the gene Glued, whose protein product shares 50% sequence identity with vertebrate dynactin and whose function is essential for viability of most (and perhaps all) cells in the organism.