Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells

Abstract

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells.

Rab10 Regulates Membrane Transport through Early Endosomes of Polarized Madin-Darby Canine Kidney Cells

“…The corresponding mutation has been found to impair GTP hydrolysis in Ras, Sec4p, Rab11a, and Rab25, thus increasing the amount of GTP-bound form of the protein (Walworth et al, 1992;Frech et al, 1994;. This mutation has been found to have dominantactive effects on the function of a variety of GTPases, with overexpression altering the function of Rab5 , Rab7 (Bucci et al, 2000), Rab8 (Ang et al, 2003), Rab14 (Jununtula et al, 2004), Rab15 (Zuk and Elferink, 1999), and Rab17 (Zacchi et al, 1994).…”

Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

“…Similar to prototypic ERα target genes, such as MYC and CCND1, RAB17, TPD52L1, and EIF3A could be new candidate genes that promote the growth or migration of ERα-positive breast cancer cells. It is noteworthy that RAB17 is a member of the Rab family of small GTPases and has been shown to be upregulated by knockdown of extracellular signal-regulated kinase (ERK) 2, which is involved in the growth, migration, and invasion of cancer cells [86] . Thus, RAB17 appears to be correlated with a favorable prognosis for ER-positive breast cancer [87] .…”

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.…”