Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking.
Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking.
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来自 1 型、2 型和 3 型赫曼斯基-普德拉克综合征患者的黑素细胞在货物运输方面具有明显的缺陷。
DOI：
10.1111/j.0022-202x.2004.23585.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Boissy,RaymondE
中科院分区：
文献类型：
--
作者：
Richmond,Bonnie;Huizing,Marjan;Knapp,Jill;Koshoffer,Amy;Zhao,Yang;Gahl,WilliamA;Boissy,RaymondE
赫曼斯基-普德拉克综合征（HPS）是一种遗传异质性疾病，其中几个基因之一的突变会中断黑素体、血小板致密体和溶酶体的生物发生。受影响的患者有眼皮肤白化病，出血素质，有时发展肉芽肿性结肠炎或肺纤维化。为了评估HPS基因在黑素体生物发生中的作用，评估了从HPS亚型1、2或3的患者培养的黑素细胞的各种黑素细胞蛋白的定位。酪氨酸酶、Tyrp 1和Dct/Tyrp 2在HPS-1和HPS-3黑素细胞中均表达，而只有酪氨酸酶在HPS-2黑素细胞中呈非典型分布。HPS 1和AP 3B 1（即，HPS-2）基因产物分别在HPS-1和HPS-2黑素细胞中不表达，而HPS-3黑素细胞显示两种蛋白质的正常表达。在正常人黑素细胞中，HPS 1蛋白表达为约80 kDa的分子，具有颗粒状和网状细胞内轮廓。在HPS-1中，溶酶体相关膜蛋白1（LAMP 1）和LAMP 3定位于异常的大颗粒;在HPS-2中，所有LAMPs均表现出正常的颗粒表达;在HPS-3中，LAMP 1和LAMP 3表现出明显的颗粒较少和絮状图案。与此相反，Rab 27，转铁蛋白和cKit的表达在所有三种HPS基因型中不受影响。这些数据表明，三种最初鉴定的人类HPS亚型在各种黑素细胞特异性蛋白的运输中表现出明显的缺陷。
Hermansky–Pudlak Syndrome (HPS) is a genetically heterogeneous disorder in which mutations in one of several genes interrupts biogenesis of melanosomes, platelet dense bodies, and lysosomes. Affected patients have oculocutaneous albinism, a bleeding diathesis, and sometimes develop granulomatous colitis or pulmonary fibrosis. In order to assess the role of HPS genes in melanosome biogenesis, melanocytes cultured from patients with HPS subtypes 1, 2, or 3 were assessed for the localization of various melanocyte proteins. Tyrosinase, Tyrp1, and Dct/Tyrp2 were atypically and distinctly expressed in HPS-1 and HPS-3 melanocytes, whereas only tyrosinase showed an atypical distribution in HPS-2 melanocytes. TheHPS1andAP3B1(i.e., HPS-2) gene products showed no expression in HPS-1 and HPS-2 melanocytes, respectively, whereas HPS-3 melanocytes exhibited normal expression for both proteins. In normal human melanocytes, the HPS1 protein was expressed as an approximately 80 kDa molecule with both granular and reticular intracellular profiles. In HPS-1, lysosome associated membrane protein 1 (LAMP1), and LAMP3 were localized to abnormal large granules; in HPS-2, all LAMPs exhibited a normal granular expression; and in HPS-3, LAMP1, and LAMP3 exhibited a distinct less granular and more floccular pattern. In contrast, the expressions of Rab 27, transferrin, and cKit were unaffected in all three HPS genotypes. These data demonstrate that the three initially identified subtypes of human HPS exhibit distinct defects in the trafficking of various melanocyte-specific proteins.
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成功培养从正常和白癜风供体获得的成人黑素细胞。
DOI：
--
发表时间：
1990
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Medrano,EE;Nordlund,JJ
通讯作者：
Nordlund,JJ
Hermansky-Pudlak 综合征黑素细胞中蛋白质定位的改变：支持 HPS 基因产物在细胞内运输中的作用。
DOI：
--
发表时间：
1998
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Boissy,RE;Zhao,Y;Gahl,WA
通讯作者：
Gahl,WA
肺纤维化的发病机制：血小板衍生生长因子先于赫曼斯基-普德拉克综合征的结构改变。
DOI：
--
发表时间：
1994
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
Harmon,KR;Witkop,CJ;White,JG;King,RA;Peterson,M;Moore,D;Tashjian,J;Marinelli,WA;Bitterman,PB
通讯作者：
Bitterman,PB
影响因子：
16
作者：
Dell'Angelica, EC;Shotelersuk, V;Bonifacino, JS
通讯作者：
Bonifacino, JS
影响因子：
3.3
作者：
Huizing, M;Sarangarajan, R;Boissy, RE
通讯作者：
Boissy, RE