BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor.
BLOC-3 mutated in Hermansky-Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor.
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DOI：
10.1016/j.cub.2012.09.020
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发表时间：
2012-11-20
期刊：
影响因子：
9.2
通讯作者：
Barr, Francis A.
中科院分区：
文献类型：
--
作者：
Gerondopoulos, Andreas;Langemeyer, Lars;Liang, Jin-Rui;Linford, Andrea;Barr, Francis A.
Hermansky-Pudlak综合征(HPS)是一种以色素部分丧失和凝血功能受损为特征的人类疾病。这些症状是由黑素小体和血小板致密颗粒的生物发生缺陷引起的，这些致密颗粒通常被称为溶酶体相关细胞器。HPS中突变的基因编码溶酶体相关细胞器复合体(BLOCK)生物发生的亚单位。BLOC-1和BLOC-2与AP-3网状蛋白接头复合体一起作用于早期内小体，将黑色素形成和黑素小体生物生成所需的成分从降解的溶酶体途径分拣到早期黑素小体。然而，Hps1-Hps4复合体BLOC-3的分子功能仍然是个谜。与其他运输途径一样，参与色素沉着的酶的黑素小体的生物发生和运输涉及特定的Rab GTP酶，在本例中为Rab32和Rab38。我们现在证明BLOC-3是一个Rab32和Rab38鸟嘌呤核苷酸交换因子(Global)。沉默BLOC-3亚基Hps1和Hps4会导致Rab32和Rab38的错误定位，并减少色素沉着。此外，我们还发现BLOC-3可以促进Rab32/38的特异性膜募集。因此，BLOC-3定义了一个在溶酶体相关细胞器的生物发生中具有特定功能的新的Rab环境基金家族。►Hps 1-Hps 4复合体(BLOC-3)是一种鸟嘌呤核苷酸交换因子，►纯化的BLOC-3对Rab32和Rab38具有特异的GEM活性。►BLOC-3可促进Rab32和Rab38重新聚集到膜►Block-3及其靶标RABS中，参与黑素小体的生物发生
Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting. These symptoms are caused by defects in the biogenesis of melanosomes and platelet dense granules, often referred to as lysosome-related organelles. Genes mutated in HPS encode subunits of the biogenesis of lysosome-related organelles complexes (BLOCs). BLOC-1 and BLOC-2, together with the AP-3 clathrin adaptor complex, act at early endosomes to sort components required for melanin formation and melanosome biogenesis away from the degradative lysosomal pathway toward early stage melanosomes. However the molecular functions of the Hps1-Hps4 complex BLOC-3 remain mysterious. Like other trafficking pathways, melanosome biogenesis and transport of enzymes involved in pigmentation involves specific Rab GTPases, in this instance Rab32 and Rab38. We now demonstrate that BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor (GEF). Silencing of the BLOC-3 subunits Hps1 and Hps4 results in the mislocalization of Rab32 and Rab38 and reduction in pigmentation. In addition, we show that BLOC-3 can promote specific membrane recruitment of Rab32/38. BLOC-3 therefore defines a novel Rab GEF family with a specific function in the biogenesis of lysosome-related organelles. ► The Hps1-Hps4 complex (BLOC-3) is a guanine nucleotide exchange factor (GEF) ► Purified BLOC-3 has specific GEF activity toward Rab32 and Rab38 ► BLOC-3 can promote recruitment of Rab32 and Rab38 to membranes ► BLOC-3 and its target Rabs act in the biogenesis of melanosomes
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影响因子：
9.2
作者：
Nordmann, Mirjana;Cabrera, Margarita;Ungermann, Christian
通讯作者：
Ungermann, Christian
影响因子：
2.5
作者：
Oiso, N;Riddle, SR;Spritz, RA
通讯作者：
Spritz, RA
DOI：
10.1083/jcb.200201003
发表时间：
2002-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ortiz D;Medkova M;Walch-Solimena C;Novick P
通讯作者：
Novick P
影响因子：
4.8
作者：
Martina, JA;Moriyama, K;Bonifacino, JS
通讯作者：
Bonifacino, JS
DOI：
10.1073/pnas.080517697
发表时间：
2000-04-11
影响因子：
11.1
作者：
Detter, JC;Zhang, Q;Kingsmore, SF
通讯作者：
Kingsmore, SF