Journal
JOURNAL OF CELL SCIENCE
Volume 116, Issue 14, Pages 2895-2906Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.00500
Keywords
Crumbs3; Pals1; PDZ domain; tight junction; polarity
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Funding
- NIDDK NIH HHS [DK58208] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07863, T32 GM07544024] Funding Source: Medline
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In Drosophila, the Crumbs-Stardust-Discs-lost complex is required during the establishment of polarized epithelia. Embryos that lack a component of this complex or overexpress Crumbs exhibit defects in epithelial morphogenesis. We recently cloned a novel mammalian epithelial Crumbs isoform, Crumbs3 (CRB3). CRB3 exists in a complex at tight junctions (TJs) with Pals1 and PATJ, the mammalian homologues of Stardust and Discs lost, respectively. Here, we observe that overexpression of CRB3 leads to delayed TJ formation in MDCK epithelial cell monolayers and disruption of polarity in MDCK cysts cultured in collagen. Both phenomena require the last four residues of CRB3. Next, we expressed, in MDCK cells, a dominant-negative Myc-Lin-2-Pals1 chimeric protein, where the PDZ domain of Lin-2 was replaced with that of Pals1. TJ and apical polarity defects were also observed in these cells. Collectively, this suggests that the CRB-Pals1 interaction is important for formation of TJs and polarized epithelia. These results provide insight into the function of the mammalian Crumbs complex during TJ formation and epithelial polarization.
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