Interaction of the p62 subunit of dynactin with Arp1 and the cortical actin cytoskeleton
Interaction of the p62 subunit of dynactin with Arp1 and the cortical actin cytoskeleton
复制标题
DOI：
10.1016/s0960-9822(00)80122-0
复制
发表时间：
1999-12-16
期刊：
影响因子：
9.2
通讯作者：
Vallee, RB
中科院分区：
文献类型：
--
作者：
Garces, JA;Clark, IB;Vallee, RB
负端定向微管运动细胞质动力蛋白靶向多种细胞内底物似乎是由一种称为动力蛋白的辅助因子介导的[1-4]。Dynactin是一种多亚基复合物，包含一个短的肌动蛋白相关蛋白1（Arp 1）细丝，在倒刺末端有capZ，在尖端有p62 [5]。p62亚基的位置和dynactin作为多功能靶向复合物的拟议作用提高了p62在动力蛋白靶向和Arp 1尖端封端中双重作用的可能性。为了进一步了解p62在动力蛋白功能中的作用，我们从大鼠脑中克隆了编码两种全长同种型蛋白质的cDNA。我们发现p62与脉孢菌属的核迁移蛋白Ropy-2同源[6];两种蛋白都含有类似于其他几种细胞骨架蛋白的LIM结构域的锌结合基序[7]。p62在培养的哺乳动物细胞中的过表达揭示了与皮质肌动蛋白、应力纤维和粘着斑位点的共定位，这些位点是微管和细胞皮质之间潜在的相互作用[8，9]。p62蛋白还与过度表达的野生型或倒钩末端突变体Arp 1的聚合物共定位，但不与尖端突变体共定位。LIM结构域的缺失废除了靶向p62的局部粘附位点，但不干扰p62与肌动蛋白或Arp 1的结合。这些数据牵连p62在Arp 1的尖端结合，并建议额外的作用，在连接动力蛋白和动力蛋白的皮质细胞骨架。(C)1999爱思唯尔科技有限公司。保留所有权利。
Targeting of the minus end directed microtubule motor cytoplasmic dynein to a wide array of intracellular substrates appears to be mediated by an accessory factor known as dynactin [1-4]. Dynactin is a multi-subunit complex that contains a short actin related protein 1 (Arp1) filament with capZ at the barbed end and p62 at the pointed end [5]. The location of the p62 subunit and the proposed role for dynactin as a multifunctional targeting complex raise the possibility of a dual role for p62 in dynein targeting and in Arp1 pointed-end capping. In order to gain further insight into the role of p62 in dynactin function, we have cloned cDNAs that encode two full-length isoforms of the protein from rat brain. We found that p62 is homologous to the nuclear migration protein Ropy-2 from Neurospora [6]; both proteins contain a zinc-binding motif that resembles the LIM domain of several other cytoskeletal proteins [7]. Overexpression of p62 in cultured mammalian cells revealed colocalization with cortical actin, stress fibers, and focal adhesion sites, sites of potential interaction between microtubules and the cell cortex [8,9]. The p62 protein also colocalized with polymers of overexpressed wild-type or barbed-end-mutant Arp1, but not with a pointed-end mutant. Deletion of the LIM domain abolished targeting of p62 to focal-adhesion sites but did not interfere with binding of p62 to actin or Arp1. These data implicate p62 in Arp1 pointed-end binding and suggest additional roles in linking dynein and dynactin to the cortical cytoskeleton. (C) 1999 Elsevier Science Ltd. All rights reserved.