Davies J P, Cotter P D, Ioannou Y A
Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Genomics. 1997 Apr 1;41(1):131-4. doi: 10.1006/geno.1997.4644.
Rab GTPases reside in specific intracellular compartments and are key regulators of vesicular transport. To facilitate studies of the mechanism of lysosomal integral membrane protein (LAMP-1) transport, cDNAs for human Rab7 and Rab9 were isolated, and their nucleotide sequences were determined. During isolation and characterization of these cDNAs a Rab9 pseudogene was identified. The sequences are highly homologous to other mammalian Rab proteins and also share homology with proteins of the Rab GTPase family. Rab7 and the Rab9 pseudogene were mapped to chromosomes 3 and 5, respectively, by amplification of their sequences from human monochromosomal somatic cell hybrids. In addition, preliminary studies using antisense expression indicate that down-regulation of either Rab7 or Rab9 proteins induces severe cell vacuolation that resembles the phenotype seen in fibroblasts from patients with Chediak-Higashi syndrome.
Rab GTP酶存在于特定的细胞内区室中，是囊泡运输的关键调节因子。为了便于研究溶酶体整合膜蛋白（LAMP-1）的运输机制，分离了人Rab7和Rab9的cDNA，并确定了它们的核苷酸序列。在这些cDNA的分离和表征过程中，鉴定出了一个Rab9假基因。这些序列与其他哺乳动物Rab蛋白高度同源，并且与Rab GTP酶家族的蛋白也有同源性。通过从人单染色体体细胞杂种中扩增Rab7和Rab9假基因的序列，分别将它们定位到染色体3和5上。此外，使用反义表达的初步研究表明，Rab7或Rab9蛋白的下调会诱导严重的细胞空泡化，类似于切-东综合征患者成纤维细胞中观察到的表型。
