Abstract
Epithelial cell junctions are essential for cell polarity, adhesion and morphogenesis. We have analysed VAB-9, a cell junction protein in Caenorhabditis elegans. VAB-9 is a predicted four-pass integral membrane protein that has greatest similarity to BCMP1 (brain cell membrane protein 1, a member of the PMP22/EMP/Claudin family of cell junction proteins) and localizes to the adherens junction domain of C. elegans apical junctions1,2,3,4. Here, we show that VAB-9 requires HMR-1/cadherin for localization to the cell membrane, and both HMP-1/α-catenin and HMP-2/β-catenin for maintaining its distribution at the cell junction. In vab-9 mutants, morphological defects correlate with disorganization of F-actin at the adherens junction; however, localization of the cadherin–catenin complex and epithelial polarity is normal. These results suggest that VAB-9 regulates interactions between the cytoskeleton and the adherens junction downstream of or parallel to α-catenin and/or β-catenin. Mutations in vab-9 enhance adhesion defects through functional loss of the cell junction genes apical junction molecule 1 (ajm-1) and discs large 1 (dlg-1), suggesting that VAB-9 is involved in cell adhesion. Thus, VAB-9 represents the first characterized tetraspan adherens junction protein in C. elegans and defines a new family of such proteins in higher eukaryotes.
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Acknowledgements
The authors wish to thank J. Priess and members of the Priess lab for providing lab space, research materials and intellectual input. We specifically thank J. Priess for suggesting the use of tetraploid strain SP346 to obtain larger embryos. We thank members of the Hardin lab, M. Labouesse, L. Bruggeman, D. Sonneborn and Joe for helpful discussions. We thank J. White and W. Mohler for assistance with MPLSM, D. Hall for advice with TEM, A. Chisholm for the vab-9 (ju6) strain, P. Heid for cosmid pools, and A. Fire for GFP and heat-shock vectors. Some of the nematode strains used in this study were provided by the Caenorhabditis Genetics Centre, which is funded by the NIH National Centre for Research Resources (NCRR). The Nematode Expression Database (http://nematode.lab.nig.ac.jp/) and some cDNA clones were provided courtesy of the laboratory of Y. Kohara at the National Institute of Genetics, Japan. This work was supported by NIH grant GM58038 (J.D.H.). J.S.S. was a Helen Hay Whitney fellow. Some funds were provided by the Gamete and Embryo Training Grant from the University of Wisconsin. The Bio-Rad MRC 1024 confocal microscope at the University of Wisconsin is supported by National Science Foundation grant 9724515.
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Simske, J., Köppen, M., Sims, P. et al. The cell junction protein VAB-9 regulates adhesion and epidermal morphology in C. elegans. Nat Cell Biol 5, 619–625 (2003). https://doi.org/10.1038/ncb1002
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DOI: https://doi.org/10.1038/ncb1002
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