Disease relevance of Rab5a

• Here, we report in a pathogenic model of L. monocytogenes (hemolysin-positive strain) that Rab5a plays a central role in Listeria destruction induced by interferon-gamma and within the phagosomal environment [1].

High impact information on Rab5a

• Removal of the entire COOH terminus by truncation (c'973 and c'991) abrogated ligand-induced Rab5a activation of endocytosis [2].
• In contrast, total contents of the rate-limiting endocytic catalysts, Rab5a and Rab7, were unaffected [3].
• Rab5a is required for early endosome fusion in vitro and regulates transport between the plasma membrane and early endosomes, in vivo [4].
• Here, we have investigated the localization and function of Rab5a in polarized epithelial cells [4].
• Active Rab5a causes remodeling of the phagosomal environment, facilitates the translocation of Rac2 to LM phagosomes, and regulates the activity of this GTPase [1].

Biological context of Rab5a

• Genetic mapping of the Rab5a and Rab5b genes on mouse Chromosomes 17 and 2, respectively [5].
• Using retroviral expression of Rab5a:S34N, a dominant negative mutant, and siRNA Rab5a silencing, we demonstrate that Rab5a is essential for the large endosome phenotype and for localization of MR in these structures [6].

Anatomical context of Rab5a

• Last, guanine nucleotide exchange on Rab5a was elevated about 3-fold in the presence of cytosol from IFN-gamma-treated cells [7].
• Confocal microscopy studies revealed that wH22xeGFP was rapidly internalized by the high-FcgammaRI-expressing cell line U937 10.6, but did not associate with intracellular proteins Rab4, Rab5a, or Lamp-1, suggesting that the targeted fusion protein was not localized in early endosomes, recycling vesicles, or lysosomes [8].
• Furthermore, we identified other regions within the RabF and RabSF motifs that are required for specific targeting of Rab27a to secretory granules or melanosomes, and Rab5a to endosomes [9].
• Lm escaped from Rab5a-negative, lysosome-associated membrane protein-1 (LAMP1)-negative, Rab7-positive, phosphatidylinositol 3-phosphate [PI(3)P]-positive vacuoles [10].

Regulatory relationships of Rab5a

• Interferon-gamma selectively induces Rab5a synthesis and processing in mononuclear cells [7].

Other interactions of Rab5a

• Interferon-gamma listericidal action is mediated by novel Rab5a functions at the phagosomal environment [1].

Analytical, diagnostic and therapeutic context of Rab5a

• IFN-gamma induced the synthesis of Rab5a in mononuclear cells as detected by immunoprecipitation and by Western blotting [7].

References