Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization.

Abstract

Abstract. The tab subfamily of small GTPases has been demonstrated to play an important role in the regulation of membrane traffic in eukaryotic cells. Compared with nonpolarized cells, epithelial cells have distinct apical and basolateral transport pathways which need to be separately regulated. This raises the question whether epithelial cells require specific rab proteins. However, all tab proteins identified so far were found to be equally expressed in polarized and nonpolarized cells. Here we report the identification of rab17, the first epithelial cell-specific small GTPase. Northern blot analysis on various mouse organs revealed that the rabl7 mRNA is present in kidney, liver, and intestine but not in organs lacking epithelial cells nor in fibroblasts. To determine whether rabl7 is specific for epithelial cells we studied its expression in the developing kidney. We found that rabl7 is absent from the mesenchymal precursors but is induced upon their differentiation into epithelial cells. In situ hybridization studies on the embryonic kidney and intestine revealed that tab17 is restricted to epithelial cells. By immunofluorescence and immunoelectron microscopy on kidney sections, rab17 was localized to the basolateral plasma membrane and to apical tubules. Rab proteins associated with two distinct compartments have been found to regulate transport between them. Therefore, our data suggest that rab17 might be involved in transcellular transport.

Nonpolarized Cells Selectively Sort Apical Proteins from Cell Surface to a Novel Compartment, but Lack Apical Retention Mechanisms

“…Multiple sets of vesicles and associated machinery were hypothesized to exist that specifically delivered cargo to each domain. Consistent with this idea, distinct apical-targeted vesicles were identified (Wandinger-Ness et al, 1990) as well as epithelial-specific, apical-targeting molecules such as annexin XIIIb and the GTPase rab17 (Lutcke et al, 1993;Fiedler et al, 1995).…”

Expression and Localization of a Novel Rab Small G Protein (Rab38) in the Rat Lung

“…No single cell expresses all of the rab family members. However, there are many Rab proteins whose expressions are ubiquitous over a variety of tissues and cells, such as Rab 1,2,4,5,[6][7][8][9][10][11][12][13][14]18,20,22,24,28, and 30. 2 Expression of some Rab proteins are highly regulated depending on cell type (epithelial, mesenchymal, or endothelial) and specific phenotype (differentiation, activation, or polarization).…”

“…Indeed, there are some Rab proteins whose roles were initially identified in this way, including Rab3 10,14 and Rab17. 12,13 Examination of the distribution of a novel Rab protein requires specific antibody with relatively high affinity. In this study, we made a rabbit anti-rat Rab38 polyclonal antibody using a C-terminal amino acid sequence.…”

Vesicular transport of Fe and interaction with other metal ions in polarized Caco2 Cell monolayers

“…Brefeldin A disrupts the Golgi apparatus (Lippincott-Schwartz et al, 1990) but also has been reported to interfere with normal sorting and recycling of the holotransferrin bound to its receptor in endocytic vesicles (Xia and Shen, 2001;van Dam and Stoorvogel, 2002). Tyrphostin A8 (AG10) inhibits a GTPase (Rab17) necessary for the fusion of vesicles and endosomes in the apical region of polarized epithelial cells (Lütcke et al, 1993;Hunziker and Peters, 1998;Zacchi et al, 1998;Knight et al, 1995;Hughson and Hopkins, 1990). This is where DMT1 (internalized from the brush border) and apotransferrin (in vesicles coming from the basal region) might come together.…”