Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome
Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome
复制标题
DOI：
10.1034/j.1600-0749.13.s8.12.x
复制
发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Feng, LJ
中科院分区：
文献类型：
--
作者：
Swank, RT;Novak, EK;Feng, LJ
Hermansky-Pudlak综合征（HPS）是一组相关的多基因隐性遗传疾病，导致三种相关细胞器的生物合成和/或功能异常；黑素体，血小板致密颗粒和溶酶体，这些依次导致色素沉着，出血延长和ceroid沉积。定位克隆策略鉴定了5个小鼠HPS基因。两种同源的人类疾病（HPS1和HPS2）也已被确定。5个小鼠基因中至少有4个编码参与调控细胞内囊泡运输的蛋白，pearl （HPS2）和mocha基因分别编码AP-3适配器复合物的β - 3a和δ亚基，AP-3适配器复合物在反式高尔基体上捕获细胞器膜蛋白。苍白基因和枪金属基因的蛋白质产物也是水泡运输机制的重要组成部分。前者与t-SNARE， syntaxin13相互作用，后者是Rab香叶基香叶基转移酶的α亚基，使Rab蛋白具有足够的亲脂性，从而在其靶膜上发挥作用。白耳（HPS1）基因编码一种功能未知的普遍表达蛋白。最近的生理学研究表明，小鼠HPS突变体和人类HPS突变体一样，寿命不同程度地缩短，并可能出现肺部异常。
Hermansky-Pudlak Syndrome (HPS) is a group of related multigenic recessively inherited disorders which causes abnormalities in the biosynthesis and/or function of three related organelles; melanosomes, platelet-dense granules and lysosomes, These lead, in turn, to hypopigmentation, prolonged bleeding and ceroid deposition. Positional cloning strategies have identified five mouse HPS genes. Two orthologous human diseases (HPS1 and HPS2) have likewise been identified. At least four of the five mouse genes encode proteins involved in the regulation of intracellular vesicle trafficking, The pearl (HPS2) and mocha genes encode the beta3A and delta subunits, respectively, of the AP-3 adaptor complex, which captures organelle membrane proteins at the trans-Golgi apparatus. The protein products of the pallid and gunmetal genes are also important components of the vesicular trafficking machinery. The former interacts with a t-SNARE, syntaxin13, and the latter is the alpha subunit of Rab geranylgeranyltransferase, which renders Rab proteins sufficiently lipophilic to function at their target membranes. The pale ear (HPS1) gene encodes a ubiquitously expressed protein of unknown function. Recent physiological studies have shown that mouse HPS mutants, Like their human HPS counterparts, have variably reduced lifespans and may have lung abnormalities.