[
Subcell Biochem,
2012]
Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ components-HMR-1/E-cadherin, HMP-2/-catenin and HMP-1/-catenin-were initially identified through genetic screens for mutants with body axis elongation defects. In early embryos, AJ proteins are found at sites of contact between blastomeres, and in epithelial cells AJ proteins localize to the multifaceted apical junction (CeAJ)-a single structure that combines the adhesive and barrier functions of vertebrate adherens and tight junctions. The apically localized polarity proteins PAR-3 and PAR-6 mediate formation and maturation of junctions, while the basolaterally localized regulator LET-413/Scribble ensures that junctions remain apically positioned. AJs promote robust adhesion between epithelial cells and provide mechanical resistance for the physical strains of morphogenesis. However, in contrast to vertebrates, C. elegans AJ proteins are not essential for general cell adhesion or for epithelial cell polarization. A combination of conserved and novel proteins localizes to the CeAJ and works together with AJ proteins to mediate adhesion.
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Semin Cell Dev Biol,
2002]
The three Caenorhabditis elegans beta-catenin each function in distinct processes: BAR-1 in canonical Wnt signaling that controls cell fates and cell migrations, HMP-2 in cell adhesion and WRM-1 in Wnt signaling pathways that function in conjunction with a mitogen-activated kinase (MAPK) pathway to control the orientations, or cell Polarities, of cells that undergo asymmetric cell divisions. In addition, WRM-1 does not interact with the canonical beta-catenin binding site in POP-1/Tcf. Thus, Wnt signaling through WRM-1 is noncanonical and, except for one division that might not include any of the three C. elegans beta-calenin, controls cell polarity in C. elegans.
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Curr Opin Cell Biol,
2012]
Cadherin superfamily proteins mediate cell-cell adhesion during development. The C. elegans embryo is a powerful system for analyzing how cadherins function in highly stereotyped morphogenetic events. In the embryo, the classical cadherin HMR-1 acts along with the Rac pathway and SAX-7/L1CAM during gastrulation. As adherens junctions mature, PAR complex proteins differentially regulate cadherin complex localization, and SRGP-1/Slit/Robo GAP aids adhesion by promoting membrane bending. Once adherens junctions form, actin is linked to the cell surface via HMP-1/-catenin, whose actin binding activity is regulated in novel ways. FMI-1/Flamingo and CDH-4/Fat-like regulate axonal morphology of both pioneer and follower neurons. C. elegans thus continues to be useful for uncovering precise functions for cadherin superfamily proteins and their associates in a simple metazoan.
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Mol Aspects Med,
2008]
The astacins are a subfamily of the metzincin superfamily of metalloproteinases. The first to be characterized was the crayfish enzyme astacin. To date more than 200 members of this family have been identified in species ranging from bacteria to humans. Astacins are involved in developmental morphogenesis, matrix assembly, tissue differentiation and digestion. Family members include the procollagen C-proteinase (BMP1, bone morphogenetic protein 1), tolloid and mammalian tolloid-like, HMP (Hydra vulgaris metalloproteinase), sea urchin BP10 (blastula protein) and SPAN (Strongylocentrotus purpuratus astacin), the ''hatching'' subfamily comprising alveolin, ovastacin, LCE, HCE (''low'' and ''high'' choriolytic enzymes), nephrosin (from carp head kidney), UVS.2 from frog, and the meprins. In the human and mouse genomes, there are six astacin family genes (two meprins, three BMP1/tolloid-like, one ovastacin), but in Caenorhabditis elegans there are 40. Meprins are the only astacin proteinases that function on the membrane and extracellularly by virtue of the fact that they can be membrane-bound or secreted. They are unique in their domain structure and covalent subunit dimerization, oligomerization propensities, and expression patterns. They are normally highly regulated at the transcriptional and post-translational levels, localize to specific membranes or extracellular spaces, and can hydrolyse biologically active peptides, cytokines, extracellular matrix (ECM) proteins and cell-surface proteins. The in vivo substrates of meprins are unknown, but the abundant expression of these proteinases in the epithelial cells of the intestine, kidney and skin provide clues to their functions.