Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5
Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5
复制标题
DOI：
10.1042/bj20082398
复制
发表时间：
2009-10-01
影响因子：
4.1
通讯作者：
Reid, Evan
中科院分区：
文献类型：
--
作者：
Edwards, Thomas L.;Clowes, Virginia E.;Reid, Evan
HSP（遗传性痉挛性截瘫）是一种遗传性疾病，其中皮质脊髓束的最长轴突远端变性，导致腿部痉挛性瘫痪。编码spartin的基因在Troyer综合征中发生突变，这是一种HSP，其中瘫痪伴有其他临床特征。斯巴达丁的亚细胞分布一直存在争议。我们在这里表明，在稳定状态下，内源性Spartin存在于胞质池，可以招募到内体和脂滴。胞质内源性Spartin是单泛素化的，我们证明了它通过PPXY基序与泛素E3连接酶AIP 4 [萎缩蛋白相互作用蛋白4; WWP 2（含WW结构域的E3泛素蛋白连接酶2）和AIP 5（WWP 1）相互作用。令人惊讶的是，PPXY基序，AIP 4和AIP 5是不需要spartin的泛素化，所以我们建议spartin作为这些蛋白质的适配器。我们的研究结果表明，spartin参与了不同的细胞功能，这可能是相关的复杂的表型中看到的Troyer综合征。
The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There has been controversy over the subcellular distribution of spartin. We show here that, at steady state, endogenous spartin exists in a cytosolic pool that can be recruited to endosomes and to lipid droplets. Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; WWP2 (WW domain-containing E3 ubiquitin protein ligase 2] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. Our results suggest that spartin is involved in diverse cellular functions, which may be of relevance to the complex phenotype seen in Troyer syndrome.