Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin.
Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin.
复制标题
Hermansky-Pudlak综合征3型蛋白与网格蛋白的关联。
DOI：
10.1186/1471-2121-6-33
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发表时间：
2005-09-13
期刊：
影响因子：
--
通讯作者：
Huizing, M
中科院分区：
文献类型：
--
作者：
Helip-Wooley, A;Westbroek, W;Dorward, H;Mommaas, M;Boissy, RE;Gahl, WA;Huizing, M
Hermansky-Pudlak综合征(HPS)是一种溶酶体相关细胞器生物发生障碍，以眼皮肤白化和出血延长为特征。这些临床表现反映了黑素细胞中的黑素小体和血小板中致密小体的形成缺陷。HPS-3型(HPS-3)是由HPS3基因突变引起的，该基因编码一个功能未知的1004个氨基酸的蛋白质，在172-176位残基上含有一个预测的笼状蛋白结合基序(LLDFE)。网状蛋白与正常黑素细胞的HPS3抗体共沉淀，而不是HPS3缺失的黑素细胞。表达GFP-HPS3融合蛋白的正常黑素细胞在20℃的温度下显示GFP-HPS3与笼状蛋白的部分共定位。GFP-HPS3(GFP-HPS3-delCBD)预测的HPS3分子中的cathrin结合区发生突变，在相同条件下不能与clathrin共定位。表达GFP-HPS3的正常黑素细胞的免疫电子显微镜显示，GFP-HPS3与网状蛋白共定位，主要分布在核周区域的小小泡上。相反，GFP-HPS3-delCBD不与笼状蛋白共定位，主要分布在细胞质中。HPS3与网状蛋白结合，主要分布在核周区含有网状蛋白的小小泡上。这种关联很可能直接通过HPS3中的功能性网状蛋白结合域发生。这些结果表明，HPS3及其蛋白复合体BLOC-2在囊泡的形成和运输中发挥了作用。
Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3) results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE) at residues 172–176. Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD) did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.
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影响因子：
7.8
作者：
GRIFFITHS, G;PFEIFFER, S;SIMONS, K;MATLIN, K
通讯作者：
MATLIN, K
影响因子：
56.9
作者：
Dell'Angelica, EC;Klumperman, J;Bonifacino, JS
通讯作者：
Bonifacino, JS
影响因子：
16
作者：
Dell'Angelica, EC;Shotelersuk, V;Bonifacino, JS
通讯作者：
Bonifacino, JS
影响因子：
30.5
作者：
Clark, RH;Stinchcombe, JC;Griffiths, GM
通讯作者：
Griffiths, GM
影响因子：
3.3
作者：
Huizing, M;Sarangarajan, R;Boissy, RE
通讯作者：
Boissy, RE