The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5)
The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5)
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DOI：
10.1111/j.1600-0854.2006.00514.x
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发表时间：
2007-02-01
期刊：
影响因子：
4.5
通讯作者：
Dell'Angelica, Esteban C.
中科院分区：
文献类型：
--
作者：
Falcon-Perez, Juan M.;Romero-Calderon, Rafael;Dell'Angelica, Esteban C.
溶酶体相关细胞器包括一组特殊的细胞内室，包括黑素体和血小板密集颗粒（哺乳动物）和眼色素颗粒（昆虫）。在人类中，这些细胞器的生物发生在统称为Hermansky-Pudlak综合征（HPS）的遗传疾病中存在缺陷。HPS-2患者和两种小鼠HPS模型携带编码适配器蛋白(AP)-3亚基的基因突变。啮齿类动物模型中发生突变的其他基因包括编码VPS33A和Rab38的基因。黑胃果蝇中所有这些基因的同源物都属于眼睛色素基因的“颗粒组”。与HPS相关的其他基因编码三种功能未知复合物的亚基，称为溶酶体相关细胞器复合物（BLOC）的生物发生-1，-2和-3，果蝇的对应物尚未被表征。在这里，我们报告了编码block -2的HPS5亚基的果蝇同源基因与颗粒群基因粉红色(p)相同，后者于1910年首次研究，但尚未在分子水平上被鉴定。AP-3亚基或VPS33A和Rab38同源基因的突变加重了粉色突变体的表型。这些结果验证了黑腹龙作为研究blos功能的遗传模型。
Lysosome-related organelles comprise a group of specialized intracellular compartments that include melanosomes and platelet dense granules (in mammals) and eye pigment granules (in insects). In humans, the biogenesis of these organelles is defective in genetic disorders collectively known as Hermansky-Pudlak syndrome (HPS). Patients with HPS-2, and two murine HPS models, carry mutations in genes encoding subunits of adaptor protein (AP)-3. Other genes mutated in rodent models include those encoding VPS33A and Rab38. Orthologs of all of these genes in Drosophila melanogaster belong to the 'granule group' of eye pigmentation genes. Other genes associated with HPS encode subunits of three complexes of unknown function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3, for which the Drosophila counterparts had not been characterized. Here, we report that the gene encoding the Drosophila ortholog of the HPS5 subunit of BLOC-2 is identical to the granule group gene pink (p), which was first studied in 1910 but had not been identified at the molecular level. The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs.