Disease relevance of Rab7

• In marked contrast, in PU.1(Pos) mAM(PU.1+) and MH-S cells, adenovirus failed to escape from endosomes, colocalized exclusively with endosome/lysosome markers (Rab5, Rab7, and Lamp1), and rarely expressed the reporter [1].
• To find out a potential relationship between the Rab7 and the atherogenesis, the same experiments were conducted with the atherosclerotic plaques obtained from rabbit and human [2].
• Diverting intracellular trafficking of Salmonella to the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide [3].
• Neither Rab7, a marker of late endosomes, nor LAMP-2 lysosomal glycoprotein was found to colocalize with polyomavirus [4].
• Disruption in the pathway prior to the acquisition of Rab7 has been suggested as playing a role in the altered maturation of Mycobacterium bovis BCG phagosomes [5].

High impact information on Rab7

• Here, we have shown that treatment of macrophages with IL-6 specifically induce the expression of Rab5 through the activation of extracellular signal-regulated kinase, whereas IL-12 exclusively upregulate the expression of Rab7 through the activation of p38 MAPK [6].
• Rab7 regulates vesicle traffic from early to late endosomes, and from late endosomes to lysosomes [7].
• In contrast, total contents of the rate-limiting endocytic catalysts, Rab5a and Rab7, were unaffected [8].
• Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase [9].
• Though their ability to fuse with late endosomes and lysosomes was virtually eliminated by wortmannin, phagosomes nevertheless recruited a sizable amount of Rab7 [9].

Biological context of Rab7

• Genetic mapping of the mouse Rab7 gene and pseudogene and of the human RAB7 homolog [10].
• The Rab7 protein is localized to the late endosomal compartment and controls late steps of endocytosis [10].
• We have mapped, by genetic linkage analysis, the mouse Rab7 gene on Chromosome (Chr) 6 and the Rab7-ps1 pseudogene on Chr 9, where the Rab7 gene has been previously reported to map [10].
• Accordingly, transfection of constitutively active Rab7 did not bypass the block of phagolysosome formation exerted by wortmannin [9].
• The role of mammalian Rab7 in autophagy is, however, unknown [11].

Anatomical context of Rab7

• Role for Rab7 in maturation of late autophagic vacuoles [11].
• The expression of Rab7 was obviously increased in the hepatic tissues, especially in the endothelial cells and hepatocytes around central veins of the high cholesterol-fed rabbit, compared to the tissues from rabbit fed a normal diet [2].
• Thus two Rab proteins regulate two different motor proteins, thereby controlling complementary phases in melanosome biogenesis: Rab7 controls microtubule-mediated transport of early and Rab27a the subsequent actin-dependent transport of mature melanosomes [12].
• A cDNA clone coding for the Rab7 protein was isolated from an NIH3T3 cell line (mouse fibroblasts) cDNA library [13].
• Here we report that removal of the carboxyl-terminal acidic Pro(505)AspGluAsnAsp(509) sequence prevents the storage of GLUT4 in the VAMP-2 positive compartment adjacent to the Golgi complex (GSC), and results in its targeting to GLUT4-positive vesicles and Rab7-positive late endosomes [14].

Associations of Rab7 with chemical compounds

• Lm escaped from Rab5a-negative, lysosome-associated membrane protein-1 (LAMP1)-negative, Rab7-positive, phosphatidylinositol 3-phosphate [PI(3)P]-positive vacuoles [15].
• Rab7 gene is up-regulated by cholesterol-rich diet in the liver and artery [2].
• Nevertheless, despite acquisition of wild-type or constitutively active Rab7, both the L. pneumophila and the M. tuberculosis phagosomes continue to exhibit altered maturation as manifested by a failure to acquire lysosome-associated membrane glycoprotein 1 [5].
• In growth factor-deprived cells, however, blocking Rab7 function prevented the clearance of glucose and amino acid transporter proteins from the cell surface [16].

Other interactions of Rab7

• Retention of Rab5 and Rab18 and selective depletion of Rab7 and Rab9 presumably enable the LSP to avoid transport to lysosomes through late endosomes [17].
• Overexpression of beta-arrestin in endothelial cells decreased colocalization with Rab7 [18].
• In Percoll gradients, ClC-5 overlapped with plasma membrane and early endosome markers, but best codistributed with the late endosomal marker, Rab7 [19].
• To gain insight into whether fusion with early endosomes is required for mycobacteria-mediated inhibition of phagosome maturation, we investigated how perturbing the GTPase cycles of Rab5 and Rab7, GTPases that regulate early and late endosome fusion, respectively, would affect phagosome maturation [20].
• The reduced content of Rab5 in the treated cells and on phagosomes inhibits the fusion of Salmonella-containing phagosomes with early endosomes, and the enhanced Rab7 content in these cells facilitated targeting of LSP to lysosomes, which contain cathepsin D and vacuolar ATPase, for killing [3].

Analytical, diagnostic and therapeutic context of Rab7

• By radiation hybrid mapping, we have located the human RAB7 gene on Chr 3, in a region homologous to the mouse Chr 6, where the Rab7 gene maps [10].
• Our experiments with quantitative electron microscopy showed that Rab7 was not needed for the initial maturation of early autophagosomes to late autophagic vacuoles, but that it participated in the final maturation of late autophagic vacuoles [11].
• Molecular cloning and expression analysis of the human Rab7 GTP-ase complementary deoxyribonucleic acid [21].
• To visualize the location of elevated Rab7 expression in tissues, patterns of the gene expression were monitored within hepatic and aortic tissues by in situ hybridization and immunohistochemistry [2].
• Western blot analysis reveals reduced Rab5 and enhanced Rab7 content in the maleylated bovine serum albumin-MDP (MBSA-MDP)-treated cells [3].

References