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J Cell Biol. 1993 May 1; 121(3): 553–564.
PMCID: PMC2119572

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


The rab 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 rab 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 rab17 mRNA is present in kidney, liver, and intestine but not in organs lacking epithelial cells nor in fibroblasts. To determine whether rab17 is specific for epithelial cells we studied its expression in the developing kidney. We found that rab17 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 rab17 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.

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Selected References

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  • Aufderheide E, Chiquet-Ehrismann R, Ekblom P. Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in the mesenchyme. J Cell Biol. 1987 Jul;105(1):599–608. [PMC free article] [PubMed]
  • Baldini G, Hohl T, Lin HY, Lodish HF. Cloning of a Rab3 isotype predominantly expressed in adipocytes. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5049–5052. [PubMed]
  • Bard JB. The development of the mouse kidney--embryogenesis writ small. Curr Opin Genet Dev. 1992 Aug;2(4):589–595. [PubMed]
  • Bartles JR, Feracci HM, Stieger B, Hubbard AL. Biogenesis of the rat hepatocyte plasma membrane in vivo: comparison of the pathways taken by apical and basolateral proteins using subcellular fractionation. J Cell Biol. 1987 Sep;105(3):1241–1251. [PMC free article] [PubMed]
  • Bomsel M, Prydz K, Parton RG, Gruenberg J, Simons K. Endocytosis in filter-grown Madin-Darby canine kidney cells. J Cell Biol. 1989 Dec;109(6 Pt 2):3243–3258. [PMC free article] [PubMed]
  • Bourne HR. Do GTPases direct membrane traffic in secretion? Cell. 1988 Jun 3;53(5):669–671. [PubMed]
  • Bucci C, Frunzio R, Chiariotti L, Brown AL, Rechler MM, Bruni CB. A new member of the ras gene superfamily identified in a rat liver cell line. Nucleic Acids Res. 1988 Nov 11;16(21):9979–9993. [PMC free article] [PubMed]
  • Bucci C, Parton RG, Mather IH, Stunnenberg H, Simons K, Hoflack B, Zerial M. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell. 1992 Sep 4;70(5):715–728. [PubMed]
  • Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell. 1990 Jul 27;62(2):317–329. [PubMed]
  • Chavrier P, Vingron M, Sander C, Simons K, Zerial M. Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line. Mol Cell Biol. 1990 Dec;10(12):6578–6585. [PMC free article] [PubMed]
  • Chavrier P, Simons K, Zerial M. The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach. Gene. 1992 Mar 15;112(2):261–264. [PubMed]
  • Christensen EI. Rapid membrane recycling in renal proximal tubule cells. Eur J Cell Biol. 1982 Nov;29(1):43–49. [PubMed]
  • Darchen F, Zahraoui A, Hammel F, Monteils MP, Tavitian A, Scherman D. Association of the GTP-binding protein Rab3A with bovine adrenal chromaffin granules. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5692–5696. [PubMed]
  • Dotti CG, Simons K. Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell. 1990 Jul 13;62(1):63–72. [PubMed]
  • Dotti CG, Parton RG, Simons K. Polarized sorting of glypiated proteins in hippocampal neurons. Nature. 1991 Jan 10;349(6305):158–161. [PubMed]
  • Ekblom P, Miettinen A, Saxén L. Induction of brush border antigens of the proximal tubule in the developing kidney. Dev Biol. 1980 Feb;74(2):263–274. [PubMed]
  • Ekblom P, Miettinen A, Virtanen I, Wahlström T, Dawnay A, Saxén L. In vitro segregation of the metanephric nephron. Dev Biol. 1981 May;84(1):88–95. [PubMed]
  • Ekblom M, Klein G, Mugrauer G, Fecker L, Deutzmann R, Timpl R, Ekblom P. Transient and locally restricted expression of laminin A chain mRNA by developing epithelial cells during kidney organogenesis. Cell. 1990 Jan 26;60(2):337–346. [PubMed]
  • Khorana HG. Rhodopsin, photoreceptor of the rod cell. An emerging pattern for structure and function. J Biol Chem. 1992 Jan 5;267(1):1–4. [PubMed]
  • Fischer von Mollard G, Mignery GA, Baumert M, Perin MS, Hanson TJ, Burger PM, Jahn R, Südhof TC. rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1988–1992. [PubMed]
  • Fischer von Mollard G, Südhof TC, Jahn R. A small GTP-binding protein dissociates from synaptic vesicles during exocytosis. Nature. 1991 Jan 3;349(6304):79–81. [PubMed]
  • Frohman MA, Dush MK, Martin GR. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. [PubMed]
  • Gorvel JP, Chavrier P, Zerial M, Gruenberg J. rab5 controls early endosome fusion in vitro. Cell. 1991 Mar 8;64(5):915–925. [PubMed]
  • Goud B, Salminen A, Walworth NC, Novick PJ. A GTP-binding protein required for secretion rapidly associates with secretory vesicles and the plasma membrane in yeast. Cell. 1988 Jun 3;53(5):753–768. [PubMed]
  • Goud B, Zahraoui A, Tavitian A, Saraste J. Small GTP-binding protein associated with Golgi cisternae. Nature. 1990 Jun 7;345(6275):553–556. [PubMed]
  • Griffiths G, McDowall A, Back R, Dubochet J. On the preparation of cryosections for immunocytochemistry. J Ultrastruct Res. 1984 Oct;89(1):65–78. [PubMed]
  • Griffiths G, Pfeiffer S, Simons K, Matlin K. Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane. J Cell Biol. 1985 Sep;101(3):949–964. [PMC free article] [PubMed]
  • GROBSTEIN C. Trans-filter induction of tubules in mouse metanephrogenic mesenchyme. Exp Cell Res. 1956 Apr;10(2):424–440. [PubMed]
  • Higgins DG, Bleasby AJ, Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. [PubMed]
  • Hopkins CR. Polarity signals. Cell. 1991 Sep 6;66(5):827–829. [PubMed]
  • Klein G, Langegger M, Timpl R, Ekblom P. Role of laminin A chain in the development of epithelial cell polarity. Cell. 1988 Oct 21;55(2):331–341. [PubMed]
  • Korhonen M, Ylänne J, Laitinen L, Virtanen I. The alpha 1-alpha 6 subunits of integrins are characteristically expressed in distinct segments of developing and adult human nephron. J Cell Biol. 1990 Sep;111(3):1245–1254. [PMC free article] [PubMed]
  • Neutra MR, Kraehenbuhl JP. Transepithelial transport and mucosal defence I: the role of M cells. Trends Cell Biol. 1992 May;2(5):134–138. [PubMed]
  • Le Bivic A, Real FX, Rodriguez-Boulan E. Vectorial targeting of apical and basolateral plasma membrane proteins in a human adenocarcinoma epithelial cell line. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9313–9317. [PubMed]
  • Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR. Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 1993 Feb;12(2):677–682. [PubMed]
  • Matter K, Brauchbar M, Bucher K, Hauri HP. Sorting of endogenous plasma membrane proteins occurs from two sites in cultured human intestinal epithelial cells (Caco-2). Cell. 1990 Feb 9;60(3):429–437. [PubMed]
  • Melançon P, Franzusoff A, Howell KE. Vesicle budding: insights from cell-free assays. Trends Cell Biol. 1991 Dec;1(6):165–171. [PubMed]
  • Milburn MV, Tong L, deVos AM, Brünger A, Yamaizumi Z, Nishimura S, Kim SH. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science. 1990 Feb 23;247(4945):939–945. [PubMed]
  • Mizoguchi A, Kim S, Ueda T, Takai Y. Tissue distribution of smg p25A, a ras p21-like GTP-binding protein, studied by use of a specific monoclonal antibody. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1438–1445. [PubMed]
  • Mizoguchi A, Kim S, Ueda T, Kikuchi A, Yorifuji H, Hirokawa N, Takai Y. Localization and subcellular distribution of smg p25A, a ras p21-like GTP-binding protein, in rat brain. J Biol Chem. 1990 Jul 15;265(20):11872–11879. [PubMed]
  • Morimoto BH, Chuang CC, Koshland DE., Jr Molecular cloning of a member of a new class of low-molecular-weight GTP-binding proteins. Genes Dev. 1991 Dec;5(12B):2386–2391. [PubMed]
  • Mostov KE, Simister NE. Transcytosis. Cell. 1985 Dec;43(2 Pt 1):389–390. [PubMed]
  • Mostov K, Apodaca G, Aroeti B, Okamoto C. Plasma membrane protein sorting in polarized epithelial cells. J Cell Biol. 1992 Feb;116(3):577–583. [PMC free article] [PubMed]
  • Nelson WJ. Regulation of cell surface polarity from bacteria to mammals. Science. 1992 Nov 6;258(5084):948–955. [PubMed]
  • Nielsen JT, Nielsen S, Christensen EI. Transtubular transport of proteins in rabbit proximal tubules. J Ultrastruct Res. 1985 Sep;92(3):133–145. [PubMed]
  • Parton RG, Prydz K, Bomsel M, Simons K, Griffiths G. Meeting of the apical and basolateral endocytic pathways of the Madin-Darby canine kidney cell in late endosomes. J Cell Biol. 1989 Dec;109(6 Pt 2):3259–3272. [PMC free article] [PubMed]
  • Peter M, Chavrier P, Nigg EA, Zerial M. Isoprenylation of rab proteins on structurally distinct cysteine motifs. J Cell Sci. 1992 Aug;102(Pt 4):857–865. [PubMed]
  • Pfeffer SR. GTP-binding proteins in intracellular transport. Trends Cell Biol. 1992 Feb;2(2):41–46. [PubMed]
  • Plutner H, Cox AD, Pind S, Khosravi-Far R, Bourne JR, Schwaninger R, Der CJ, Balch WE. Rab1b regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. J Cell Biol. 1991 Oct;115(1):31–43. [PMC free article] [PubMed]
  • Rodman JS, Mercer RW, Stahl PD. Endocytosis and transcytosis. Curr Opin Cell Biol. 1990 Aug;2(4):664–672. [PubMed]
  • Rodriguez-Boulan E, Nelson WJ. Morphogenesis of the polarized epithelial cell phenotype. Science. 1989 Aug 18;245(4919):718–725. [PubMed]
  • Salminen A, Novick PJ. A ras-like protein is required for a post-Golgi event in yeast secretion. Cell. 1987 May 22;49(4):527–538. [PubMed]
  • Saxén L, Saksela E. Transmission and spread of embryonic induction. II. Exclusion of an assimilatory transmission mechanism in kidney tubule induction. Exp Cell Res. 1971 Jun;66(2):369–377. [PubMed]
  • Saxén L, Koskimies O, Lahti A, Miettinen H, Rapola J, Wartiovaara J. Differentiation of kidney mesenchyme in an experimental model system. Adv Morphog. 1968;7:251–293. [PubMed]
  • Schnabel E, Anderson JM, Farquhar MG. The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. J Cell Biol. 1990 Sep;111(3):1255–1263. [PMC free article] [PubMed]
  • Schoenenberger CA, Matlin KS. Cell polarity and epithelial oncogenesis. Trends Cell Biol. 1991 Oct;1(4):87–92. [PubMed]
  • Segev N, Mulholland J, Botstein D. The yeast GTP-binding YPT1 protein and a mammalian counterpart are associated with the secretion machinery. Cell. 1988 Mar 25;52(6):915–924. [PubMed]
  • Simons K, Fuller SD. Cell surface polarity in epithelia. Annu Rev Cell Biol. 1985;1:243–288. [PubMed]
  • Simons K, Wandinger-Ness A. Polarized sorting in epithelia. Cell. 1990 Jul 27;62(2):207–210. [PubMed]
  • Sorokin L, Sonnenberg A, Aumailley M, Timpl R, Ekblom P. Recognition of the laminin E8 cell-binding site by an integrin possessing the alpha 6 subunit is essential for epithelial polarization in developing kidney tubules. J Cell Biol. 1990 Sep;111(3):1265–1273. [PMC free article] [PubMed]
  • Touchot N, Chardin P, Tavitian A. Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8210–8214. [PubMed]
  • Vainio S, Lehtonen E, Jalkanen M, Bernfield M, Saxén L. Epithelial-mesenchymal interactions regulate the stage-specific expression of a cell surface proteoglycan, syndecan, in the developing kidney. Dev Biol. 1989 Aug;134(2):382–391. [PubMed]
  • Valencia A, Chardin P, Wittinghofer A, Sander C. The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry. 1991 May 14;30(19):4637–4648. [PubMed]
  • Van Der Sluijs P, Hull M, Zahraoui A, Tavitian A, Goud B, Mellman I. The small GTP-binding protein rab4 is associated with early endosomes. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6313–6317. [PubMed]
  • van der Sluijs P, Hull M, Webster P, Mâle P, Goud B, Mellman I. The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway. Cell. 1992 Sep 4;70(5):729–740. [PubMed]
  • van Deurs B, Christensen EI. Endocytosis in kidney proximal tubule cells and cultured fibroblasts: a review of the structural aspects of membrane recycling between the plasma membrane and endocytic vacuoles. Eur J Cell Biol. 1984 Jan;33(1):163–173. [PubMed]
  • Vestweber D, Kemler R, Ekblom P. Cell-adhesion molecule uvomorulin during kidney development. Dev Biol. 1985 Nov;112(1):213–221. [PubMed]
  • Vielh E, Touchot N, Zahraoui A, Tavitian A. Nucleotide sequence of a rat cDNA: rab1B, encoding a rab1-YPT related protein. Nucleic Acids Res. 1989 Feb 25;17(4):1770–1770. [PMC free article] [PubMed]
  • Wandinger-Ness A, Bennett MK, Antony C, Simons K. Distinct transport vesicles mediate the delivery of plasma membrane proteins to the apical and basolateral domains of MDCK cells. J Cell Biol. 1990 Sep;111(3):987–1000. [PMC free article] [PubMed]
  • Weller A, Beck S, Ekblom P. Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis. J Cell Biol. 1991 Jan;112(2):355–362. [PMC free article] [PubMed]
  • Wilson DB, Wilson MP. Identification and subcellular localization of human rab5b, a new member of the ras-related superfamily of GTPases. J Clin Invest. 1992 Mar;89(3):996–1005. [PMC free article] [PubMed]
  • Wilson DW, Whiteheart SW, Orci L, Rothman JE. Intracellular membrane fusion. Trends Biochem Sci. 1991 Sep;16(9):334–337. [PubMed]
  • Zahraoui A, Touchot N, Chardin P, Tavitian A. The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. J Biol Chem. 1989 Jul 25;264(21):12394–12401. [PubMed]
  • Zerial M, Parton R, Chavrier P, Frank R. Localization of Rab family members in animal cells. Methods Enzymol. 1992;219:398–407. [PubMed]
  • Zurzolo C, Le Bivic A, Quaroni A, Nitsch L, Rodriguez-Boulan E. Modulation of transcytotic and direct targeting pathways in a polarized thyroid cell line. EMBO J. 1992 Jun;11(6):2337–2344. [PubMed]

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