Key points are not available for this paper at this time.
dCrumbs is an apical organizer crucial for the maintenance of epithelial polarity in Drosophila(1Knust E. Curr. Opin. Genet. Dev. 2000; 10: 471-475Crossref PubMed Scopus (49) Google Scholar). It is known that dCrumbs interacts with Discs lost (Dlt), a protein with four PDZ (PSD95/Discs Large/ZO-1) domains (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar), and Stardust (Sdt), a protein of the MAGUK (membrane-associated guanylate kinase) family (3Hong Y. Stronach B. Perrimon N. Jan L.Y. Jan Y.N. Nature. 2001; 414: 634-638Crossref PubMed Scopus (202) Google Scholar, 4Bachmann A. Schneider M. Theilenberg E. Grawe F. Knust E. Nature. 2001; 414: 638-643Crossref PubMed Scopus (235) Google Scholar). We have searched for potential homologs of Dlt in human epithelial cells and characterized one of them in intestinal epithelial cells. Human INAD-like (hINADl) contains 8 PDZ domains, is concentrated in tight junctions, and is also found at the apical plasma membrane. Overexpression of hINADl disrupted the tight junctions localization of ZO-1 and 3. We also identified a partial cDNA coding the transmembrane and cytoplasmic domains of a new human crumbs (CRB3) expressed in Caco-2 cells. This CRB3 was able to interact through its C-terminal end with the N-terminal domain of hINADl. Taken together, the data indicate that hINADl is likely to represent a Dlt homolog in mammalian epithelial cells and might be involved in regulating the integrity of tight junctions. We thus propose to rename hINADl PATJ for proteinassociated to tight junctions. dCrumbs is an apical organizer crucial for the maintenance of epithelial polarity in Drosophila(1Knust E. Curr. Opin. Genet. Dev. 2000; 10: 471-475Crossref PubMed Scopus (49) Google Scholar). It is known that dCrumbs interacts with Discs lost (Dlt), a protein with four PDZ (PSD95/Discs Large/ZO-1) domains (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar), and Stardust (Sdt), a protein of the MAGUK (membrane-associated guanylate kinase) family (3Hong Y. Stronach B. Perrimon N. Jan L.Y. Jan Y.N. Nature. 2001; 414: 634-638Crossref PubMed Scopus (202) Google Scholar, 4Bachmann A. Schneider M. Theilenberg E. Grawe F. Knust E. Nature. 2001; 414: 638-643Crossref PubMed Scopus (235) Google Scholar). We have searched for potential homologs of Dlt in human epithelial cells and characterized one of them in intestinal epithelial cells. Human INAD-like (hINADl) contains 8 PDZ domains, is concentrated in tight junctions, and is also found at the apical plasma membrane. Overexpression of hINADl disrupted the tight junctions localization of ZO-1 and 3. We also identified a partial cDNA coding the transmembrane and cytoplasmic domains of a new human crumbs (CRB3) expressed in Caco-2 cells. This CRB3 was able to interact through its C-terminal end with the N-terminal domain of hINADl. Taken together, the data indicate that hINADl is likely to represent a Dlt homolog in mammalian epithelial cells and might be involved in regulating the integrity of tight junctions. We thus propose to rename hINADl PATJ for proteinassociated to tight junctions. zonula adherens Madin-Darby canine kidney human inactivation no after potential D-like zonula occludens tight junctions septate junctions Discs lost multi-PDZ-domain protein atypical protein kinase C dipeptidyl peptidase IV vesicular stomatitis virus protein G protein associated to tight junctions reverse transcriptase new human crumbs membrane-associated guanylate kinase Stardust Drosophila The polarized organization of epithelial cells is a fundamental process in animal development and the use of genetics inDrosophila has made a significant contribution to the understanding of some of the mechanisms involved in epithelial polarity (for recent reviews, see Refs. 1Knust E. Curr. Opin. Genet. Dev. 2000; 10: 471-475Crossref PubMed Scopus (49) Google Scholar, 5Knoblich J.A. Curr. Biol. 2000; 10: R791-R794Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, and 6Kramer H. J. Cell Biol. 2000; 151: F15-F18Crossref PubMed Scopus (5) Google Scholar). This approach has led to the identification of Armadillo (7Peifer M. McCrea P.D. Green K.J. Wieschaus E. Gumbiner B.M. J. Cell Biol. 1992; 118: 681-691Crossref PubMed Scopus (306) Google Scholar), Discs Large(8Woods D.F. Hough C. Peel D. Callaini G. Bryant P.J. J. Cell Biol. 1996; 134: 1469-1482Crossref PubMed Scopus (351) Google Scholar), and Scribble (9Bilder D. Perrimon N. Nature. 2000; 403: 676-680Crossref PubMed Scopus (551) Google Scholar), to name a few of the genes regulating epithelial cell shape and polarity. Among the protein complexes that have been identified as playing a major role in creating or maintaining epithelial cell polarity in Drosophila, the dCrumbs (Crumbs) complex remains the only one localized on the apical side of the epidermal cells (10Tepass U. Theres C. Knust E. Cell. 1990; 61: 787-799Abstract Full Text PDF PubMed Scopus (547) Google Scholar). Embryos mutant for crumbs die after gastrulation with severe defects in epidermal cell polarity (11Wodarz A. Hinz U. Engelbert M. Knust E. Cell. 1995; 82: 67-76Abstract Full Text PDF PubMed Scopus (547) Google Scholar) because of a failure to assemble a zonula adherens (ZA)1 from spot adherens junctions (12Tepass U. Dev. Biol. 1996; 177: 217-225Crossref PubMed Scopus (201) Google Scholar, 13Grawe F. Wodarz A. Lee B. Knust E. Skaer H. Development. 1996; 122: 951-959PubMed Google Scholar). Thus, dCrumbs, which is localized on the apical side of the ZA, controls its assembly and positioning during gastrulation. Its cytoplasmic domain, which contains 37 amino acids, mediates this important function. In fact one of the loss-of-function alleles of crumbs (8F105) is a stop mutation that prevents the translation of the last 23 amino acids (10Tepass U. Theres C. Knust E. Cell. 1990; 61: 787-799Abstract Full Text PDF PubMed Scopus (547) Google Scholar). Recently, a gene named Discs lost (dlt) was shown to have a crucial role in epithelial polarization (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar), and the protein Dlt is also localized to the subapical region where dCrumbs is concentrated. Indeed, Dlt interacts by the first of its four PDZ (PSD95/Discs Large/ZO-1) domains (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar) with the C-terminal four amino acids ERLI of the dCrumbs cytoplasmic domain (14Klebes A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). Thus, the dCrumbs-Dlt complex is a key component regulating cell polarity probably by controlling the assembly and positioning of the ZA in Drosophila epidermal cells. The presence of four PDZ domains in Dlt enables it to build a protein complex serving as a scaffold whose ultimate function would be to direct the assembly of E-cadherin and other components to their correct positions in the membrane. Although the identification of the dCrumbs complex inDrosophila has shed light on epithelial organization, very little is known about the conservation of such a complex in vertebrates. First, the organization of the junctional complexes is different between arthropods and vertebrates because the latter possesses tight junctions (TJs) localized just apical to the ZA, whereas the former establish septate junctions (SJs) basolateral to the ZA (1Knust E. Curr. Opin. Genet. Dev. 2000; 10: 471-475Crossref PubMed Scopus (49) Google Scholar). Tight junctions are made of transmembrane proteins such as claudins and occludins and septate junctions contain neurexin IV. SJs recruit cytoplasmic proteins like Discs Large, Coracle, and Scribble, whereas TJs have ZO-1, -2, -3, and cingulin as peripheral proteins (for a recent review, see Ref. 15Zahraoui A. Louvard D. Galli T. J. Cell Biol. 2000; 151: F31-F36Crossref PubMed Scopus (161) Google Scholar). Thus, while performing the sealing of the epithelial monolayer SJs and TJs can be considered as distinct molecular entities. It has been proposed that the subapical region (or marginal zone) of epithelial cells in Drosophila can be compared to some extent to TJs of vertebrates (1Knust E. Curr. Opin. Genet. Dev. 2000; 10: 471-475Crossref PubMed Scopus (49) Google Scholar). In fact, some of the proteins found in this subapical region like Par-3 (Bazooka) and an atypical protein kinase C (aPKC) are also localized at the TJs (16Wodarz A. Ramrath A. Grimm A. Knust E. J. Cell Biol. 2000; 150: 1361-1374Crossref PubMed Scopus (376) Google Scholar,17Izumi Y. Hirose T. Tamai Y. Hirai S. Nagashima Y. Fujimoto T. Tabuse Y. Kemphues K.J. Ohno S. J. Cell Biol. 1998; 143: 95-106Crossref PubMed Scopus (439) Google Scholar). If this hypothesis is true, a protein complex homolog to the dCrumbs complex should also be localized to the TJs in mammalian epithelial cells. Interestingly, a human homolog of Crumbs, called CRB1, was cloned from patients suffering from retinitis pigmentosa 12, but the isolated cDNA lacked a transmembrane and cytoplasmic domain (18den Hollander A.I. ten Brink J.B. de Kok Y.J. van Soest S. van den Born L.I. van Driel M.A. van de Pol D.J. Payne A.M. Bhattacharya S.S. Kellner U. Hoyng C.B. Westerveld A. Brunner H.G. Bleeker- Wagemakers E.M. Deutman A.F. Heckenlively J.R. Cremers F.P. Bergen A.A. Nat. Genet. 1999; 23: 217-221Crossref PubMed Scopus (384) Google Scholar). No homolog of Dlt has yet been described and therefore the existence of a conserved complex in vertebrates is unknown. To answer this question, have searched for homologs of Dlt in human epithelial cells the first PDZ domain of which was to the cytoplasmic of dCrumbs (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar). We have identified human proteins with a conserved PDZ domain, C. A. H. 1998; PubMed Scopus Google Scholar) and hINADl S. PubMed Scopus Google Scholar) and have characterized one of hINADl. hINADl was localized to the apical and was concentrated at the of the TJs in Caco-2 and epithelial cells. Overexpression of hINADl in cells disrupted the localization of TJs and In hINADl with a new human expressed in epithelial in which the domain was by a vesicular stomatitis virus protein G This involved the N-terminal region of hINADl and the C-terminal region of the CRB3 cytoplasmic a complex to the one found in Drosophila can the function of TJs in mammalian epithelial cells the where is was ZO-1 and a from and from D. Louvard dipeptidyl peptidase IV was a from A. and has been characterized A. H. J. Cell Biol. Google Scholar). was from and was from and was from was at a of and for and hINADl and and by the of a hINADl and also to to the hINADl and by the or of hINADl and the of in from and in to the Caco-2 cells from A. and as described M. C. A. H. A. J. Cell PubMed Google Scholar) with Caco-2 and cells and isolated of and for by after The of was for in cells hINADl and cloned by the and Caco-2 and was with the hINADl with a by in and The was by a C-terminal dCrumbs the transmembrane domain, and cytoplasmic domain of dCrumbs acids and it the the from This was of Human cytoplasmic domains with the the and for CRB1, and for and for to the of the on and as described J. A. J. Cell 2000; PubMed Google Scholar). was a of Caco-2 cells and human and as described H. A. S. S. D. J. D. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). as described C. A. J. Cell PubMed Google Scholar) human from whereas was from Caco-2 cells and as described A. E. U. S. A. PubMed Scopus Google Scholar). cells in and at with and by and To potential human homologs of Dlt searched for proteins with a PDZ domain the first PDZ domain of which is involved in Drosophila (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar). We found human hINADl S. PubMed Scopus Google Scholar) and C. A. H. 1998; PubMed Scopus Google Scholar), with a PDZ domain that is conserved proteins only PDZ domains and that to as scaffold proteins with no The first PDZ domains of hINADl and are whereas the PDZ domains and 8 of hINADl PDZ domains and of The of in human has been C. A. H. 1998; PubMed Scopus Google Scholar), and a is in and other of and are also in some of We a of hINADl in human and found that a major of was expressed in the and of was also in In Caco-2 cells at and that of hINADl expressed in cells from human of hINADl was with by This was to human and Caco-2 and with for by the are on the is known about the role or of the region acids between PDZ domains and which is the conserved region of this and the N-terminal domain acids protein and by on from epithelial cell and human the domain, hINADl a complex with in and Caco-2 cells and also in human and The and of them and in and the was in Caco-2 cells The the N-terminal region the molecular and in that the has a different for of of different molecular likely represent of hINADl because in the cDNA data at with or with different for translation To this hypothesis some of are H. S. J. Y. T. S. N. A. T. 2001; PubMed Scopus Google Scholar), and at in Caco-2 cells by and by We that some of the are or This hypothesis is by the fact that expressed cells a hINADl with a in Caco-2 only one with few the It is that of at a molecular of the at about which be because of a shape or with hINADl the in that hINADl for the N-terminal in Thus, be a complex of hINADl gene in epithelial but yet its the of hINADl with the that a potential homolog of Dlt should be membrane-associated because Dlt is found in the cells. and A. of hINADl found associated with the of Caco-2 and human cells with the of the which was also found in the to hINADl in Caco-2 cells and in cells Caco-2 cells in that hINADl was at that it might with junctions In hINADl with a of TJs in epithelial cells M. T. M. A. S. S. J. Cell Biol. PubMed Scopus Google Scholar), and with a of the apical of intestinal cells A. K.J. Dev. Biol. PubMed Scopus Google Scholar). No was with a basolateral A. H. J. Cell Biol. Google Scholar). This was also in cells with the the first that the protein was hINADl The of was on of human that hINADl was associated with the apical plasma and the tight junctions complex in To the between hINADl and with on of Caco-2 cells and human In cell hINADl was associated with tight junctions, with the apical and was also localized the apical plasma and in the a that the proteins in that hINADl was associated with TJs To it was hINADl that was in the TJs and a protein with the a coding for hINADl and with a was expressed in Caco-2 cells and localized the expressed at this concentrated at the TJs where it with ZO-1 that hINADl is of the TJs We the of of on the integrity of TJs in epithelial cells. cells with or with a in which the first PDZ domains In cells the of ZO-1 and was disrupted to partial or of peripheral of apical or basolateral and of was data indicate that cell polarity and by of No of the ZO-1 and was with the the Thus, of at of the TJs was but the of epithelial cell was of in cells. was expressed in and the cells with the in and the or in that cells have a disrupted of compared with cells. of at the of that cells have a disrupted of ZO-1 and compared with indicate We hINADl is a potential homolog of Dlt in mammalian epithelial cells by its to interact with We a in which the domain of Drosophila was by a only the the and the cytoplasmic domains this was expressed in it was to the plasma and thus be to potential with hINADl. was from the the for the presence of while cells as a hINADl with that it interact like Dlt with inDrosophila (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar, A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). the between dCrumbs and Dlt the last amino acids of dCrumbs cytoplasmic also expressed a mutant of This mutant the last 23 and as a in Drosophila A. Grawe F. Knust E. Dev. PubMed Scopus Google Scholar). that the between the proteins the of the dCrumbs cytoplasmic The hINADl was also as a and was with that it is hINADl that interacts with dCrumbs and a protein by yet no human expressed in epithelial cells has been searched human with the cytoplasmic of Drosophila and found different human was (18den Hollander A.I. ten Brink J.B. de Kok Y.J. van Soest S. van den Born L.I. van Driel M.A. van de Pol D.J. Payne A.M. Bhattacharya S.S. Kellner U. Hoyng C.B. Westerveld A. Brunner H.G. Bleeker- Wagemakers E.M. Deutman A.F. Heckenlively J.R. Cremers F.P. Bergen A.A. Nat. Genet. 1999; 23: 217-221Crossref PubMed Scopus (384) Google Scholar), whereas the other are new gene and and the conserved from the and the four last amino acids, for dCrumbs function in Drosophila (14Klebes A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). for human Crumbs, with from Caco-2 cells 8 and found that CRB3 was expressed in cells and be the of hINADl in epithelial cells. We therefore expressed a the as an domain, the transmembrane domain of dCrumbs, and CRB3 cytoplasmic This was able to in cells a of the last four amino acids, 8 CRB3 can interact with hINADl in To the domain of hINADl that interacts with CRB3 of of the first N-terminal amino acids or the domain To was able to interact with but with that the between hINADl and CRB3 was by an hINADl PDZ domain as was for dCrumbs and Dlt (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar). hINADl was cloned by to Drosophila S. PubMed Scopus Google Scholar), where is a key protein in inDrosophila and of PDZ domains B. 1995; Full Text PDF PubMed Scopus Google Scholar). Its to is as as the found between hINADl and PDZ domains of Dlt can be on PDZ domains of hINADl with from to PDZ domains of on the other and with PDZ domains of hINADl. It is thus that hINADl is an of but is a mammalian protein the Dlt four PDZ domains and a C-terminal region with at PDZ domains, which function. This is by the existence of a domain that is to hINADl. The organization of which is of and PDZ domains, that the proteins have from the Although known of have been described A. A. M. H. T. 2000; PubMed Scopus Google Scholar, Lee S.S. J. Cell. 2000; PubMed Scopus Google Scholar, C. A. S. A. E. J. H. C. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), no protein to hINADl has yet been the molecular associated with hINADl to its role in epithelial organization and We also propose to its name to PATJ associated to tight to dCrumbs is a transmembrane protein for the correct positioning and assembly of the ZA in cells F. Wodarz A. Lee B. Knust E. Skaer H. Development. 1996; 122: 951-959PubMed Google Scholar, U. Dev. Biol. 1996; 177: 217-225Crossref PubMed Scopus (201) Google Scholar). dCrumbs to the subapical region (or marginal zone) of epithelial cells just the ZA and interacts with a protein called Dlt (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar) and a MAGUK protein named Stardust (3Hong Y. Stronach B. Perrimon N. Jan L.Y. Jan Y.N. Nature. 2001; 414: 634-638Crossref PubMed Scopus (202) Google Scholar, 4Bachmann A. Schneider M. Theilenberg E. Grawe F. Knust E. Nature. 2001; 414: 638-643Crossref PubMed Scopus (235) Google Scholar). hypothesis is that by Dlt and dCrumbs a of the complex found in the ZA (14Klebes A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). localized to this like Scribble, are also involved in positioning components of the ZA (9Bilder D. Perrimon N. Nature. 2000; 403: 676-680Crossref PubMed Scopus (551) Google Scholar). of the genes and proteins involved in the of cell polarity inDrosophila have been described in vertebrates (for review, see Ref. 15Zahraoui A. Louvard D. Galli T. J. Cell Biol. 2000; 151: F31-F36Crossref PubMed Scopus (161) Google Scholar), that mechanisms are in mammalian epithelial cells. It be that in the ZA is by the zonula which the TJs J. Cell 1998; PubMed Google Scholar) in SJs the an about the existence in epithelial cells of a protein complex homolog to dCrumbs Recently, a gene was described in human as for some of retinitis pigmentosa (18den Hollander A.I. ten Brink J.B. de Kok Y.J. van Soest S. van den Born L.I. van Driel M.A. van de Pol D.J. Payne A.M. Bhattacharya S.S. Kellner U. Hoyng C.B. Westerveld A. Brunner H.G. Bleeker- Wagemakers E.M. Deutman A.F. Heckenlively J.R. Cremers F.P. Bergen A.A. Nat. Genet. 1999; 23: 217-221Crossref PubMed Scopus (384) Google Scholar), and the cytoplasmic domain of this was able to inDrosophila Hollander A.I. de Kok Y.J. A. Brunner H.G. Knust E. Cremers F.P. Genet. 2001; 10: PubMed Scopus Google Scholar). It is expressed in epithelial and no other dCrumbs homologs have been and have been in and while for potential homologs of have found that PATJ that indicate it is a PATJ is a protein that like no other domain, and its PDZ domain is to Dlt PDZ domain PDZ domain of Dlt to the cytoplasmic of dCrumbs (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar), that its mammalian which also human This potential was by the of dCrumbs and a new human Crumbs, to PATJ in a it was on the presence of the C-terminal amino acids ERLI of cytoplasmic domain as is the inDrosophila (14Klebes A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). PATJ interacts with CRB3 through its N-terminal region because its to PDZ domain from this because a PATJ this domain to the molecular of the of PATJ to human might have from in Drosophila (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar). it is likely that the between CRB3 and PATJ is and is by a human homolog of PATJ is only membrane-associated but is also localized to the of the subapical where Dlt is concentrated in Drosophila (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar, G. C. J. U. J. Cell Biol. 2000; 151: PubMed Scopus Google Scholar). Dlt is also found in the apical in and see an apical in Caco-2 and cells with different PATJ with TJs and the apical was by In Drosophila, the of Dlt led to epithelial cell and partial of polarity by of the ZA (2Bhat M.A. Izaddoost S., Lu, Y. Cho K.O. Choi K.W. Bellen H.J. Cell. 1999; 96: 833-845Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar). The fact that of PATJ also TJs localization of ZO-1 and that it be a homolog of No of the cell polarity was that by is to to the of We have that the of of PATJ is during the of cell This that PATJ is important for the of TJs by some of its components to the correct in the cells and The role of PATJ in the and maintenance of the TJs remains but the identification of some of its to its role in that PATJ contains at 8 PDZ domains PATJ can to and is likely to build a at the of the PATJ is a new protein associated with the and it this because other proteins with PDZ domains have been shown to be associated with In is a complex that the localization inDrosophila and in the and This complex is localized to the apical and subapical region in Drosophila (16Wodarz A. Ramrath A. Grimm A. Knust E. J. Cell Biol. 2000; 150: 1361-1374Crossref PubMed Scopus (376) Google Scholar) and to TJs in Y. Hirose T. Tamai Y. Hirai S. Nagashima Y. Fujimoto T. Tabuse Y. Kemphues K.J. Ohno S. J. Cell Biol. 1998; 143: 95-106Crossref PubMed Scopus (439) Google Scholar) and was shown to be involved in the organization of TJs and in epithelial cell polarization A. T. Hirose T. N. M. Y. T. Ohno S. J. Cell Biol. 2001; PubMed Scopus Google Scholar, S. Curr. Opin. Cell Biol. 2001; PubMed Scopus Google Scholar). No has been found yet between this complex and dCrumbs in the protein complexes are and be a major in the The other of the complex in epithelial cells to be but the fact that human with different cytoplasmic in and that them CRB3 is expressed in Caco-2 cells to a conservation of the CRB3 has a conserved cytoplasmic domain compared with dCrumbs and the amino acids and that to be for the function of (14Klebes A. Knust E. Curr. Biol. 2000; 10: 76-85Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). In it is to that CRB3 is the only human that also has a that to an or a domain and thus be in have been able to CRB3 that to its localization to that it is with PATJ in epithelial cells. The of a cDNA with an should to this The of the role of protein in the complex to the of Crumbs, and We E. Knust for dCrumbs cDNA and for J. for and during this C. for intestinal and B. for We B. for with
Lemmers et al. (Mon,) studied this question.
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