Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels
Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels
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DOI：
10.1128/mcb.24.11.4979-4993.2004
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Pendergast, AM
中科院分区：
文献类型：
--
作者：
Echarri, A;Lai, MJ;Pendergast, AM
Abl相互作用子1（Abl interactor 1，Abi-1）蛋白参与肌动蛋白动力学的调节，并且定位于板状伪足和丝状伪足的尖端。在这里，我们表明，阿比特龙-1结合肌动蛋白成核蛋白波-1通过氨基末端波结合（WAB）域和阿比特龙-1-波-1相互作用的破坏防止阿比特龙-1到达尖端的片状伪足。Abi-1与Wave-1的Wave同源结构域结合，该区域是Wave-1易位至板状伪足所需的。缺乏Abi-1的一个等位基因并且对于相关Abi-2蛋白是纯合无效的小鼠胚胎成纤维细胞表现出降低的Wave-1蛋白水平。这种表型被保留Wave-1结合的Abi-1蛋白拯救，但不能被不能结合Wave-1的Abi-1突变体拯救。此外，我们在Abi-1的氨基末端发现了一个重叠的SNARE结构域，该结构域与SNARE家族成员Syntaxin-1相互作用。此外，我们证明，阿比特龙-1穿梭进出细胞核中的一个来普霉素B（LMB）依赖性的方式和阿比特龙-1在LMB的情况下，需要的SNARE，WA B，和SH 3结构域的组合失活的阿比特龙-1的完全核转位。因此，阿比特龙-1经历核质穿梭和功能的前沿，以调节波-1定位和蛋白质水平。
The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of actin dynamics and localizes to the tips of lamellipodia and filopodia. Here, we show that Abi-1 binds the actin nucleator protein Wave-1 through an amino-terminal Wave-binding (WAB) domain and that disruption of the Abi-1-Wave-1 interaction prevents Abi-1 from reaching the tip of the lamellipodium. Abi-1 binds to the Wave homology domain of Wave-1, a region that is required for translocation of Wave-1 to the lamellipodium. Mouse embryo fibroblasts that lack one allele of Abi-1 and are homozygous null for the related Abi-2 protein exhibit decreased Wave-1 protein levels. This phenotype is rescued by Abi-1 proteins that retain Wave-1 binding but not by Abi-1 mutants that cannot bind to Wave-1. Moreover, we uncovered an overlapping SNARE domain in the amino terminus of Abi-1 that interacts with Syntaxin-1, a SNARE family member. Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1. Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels.