DLG-1 Is a MAGUK Similar to SAP97 and Is Required for Adherens Junction Formation

Abstract

Cellular junctions are critical for intercellular communication and for the assembly of cells into tissues. Cell junctions often consist of tight junctions, which form a permeability barrier and prevent the diffusion of lipids and proteins between cell compartments, and adherens junctions, which control the adhesion of cells and link cortical actin filaments to attachment sites on the plasma membrane. Proper tight junction formation and cell polarity require the function of membrane-associated guanylate kinases (MAGUKs) that contain the PDZ protein-protein interaction domain. In contrast, less is known about how adherens junctions are assembled. Here we describe how the PDZ-containing protein DLG-1 is required for the proper formation and function of adherens junctions in Caenorhabditis elegans. DLG-1 is a MAGUK protein that is most similar in sequence to mammalian SAP97, which is found at both synapses of the CNS, as well as at cell junctions of epithelia. DLG-1 is localized to adherens junctions, and DLG-1 localization is mediated by an amino-terminal domain shared with SAP97 but not found in other MAGUK family members. DLG-1 recruits other proteins and signaling molecules to adherens junctions, while embryos that lack DLG-1 fail to recruit the proteins AJM-1 and CPI-1 to adherens junctions. DLG-1 is required for the proper organization of the actin cytoskeleton and for the morphological elongation of embryos. In contrast to other proteins that have been observed to affect adherens junction assembly and function, DLG-1 is not required to maintain cell polarity. Our results suggest a new function for MAGUK proteins distinct from their role in cell polarity. INTRODUCTIONCell adhesion facilitates the assembly of individual cells into organized tissues, and several different cell adhesion mechanisms fulfill this role (Gumbiner, 1996). One of these adhesion mechanisms is the formation of the tight junction or zonula occludens, which functions to regulate the permeability of the cell layer and to polarize the cell surface into apical and basolateral compartments (Mitic and Anderson, 1998). Tight junctions (in vertebrates) and septate junctions (in invertebrates) maintain the separation between the apical and basolateral surfaces by hindering the diffusion of lipids and proteins (Powell, 1981;Gumbiner, 1987). In contrast to tight junctions, a second mechanism of cell adhesion is the adherens junction, which is responsible for maintaining adhesion between neighboring cells and is important for intercellular communication (Muller, 2000;Vasioukhin and Fuchs, 2001).While many proteins have important roles in assembling these junctions, mutations in these proteins result in large defects in cell polarity as well. For example, mutations in the Drosophila genes bazooka (baz), crumbs (crb), discs lost (dlt), scribble (scrib), lethal (1) discs large (dlg), and lethal giant larvae (lgl), and the Caenorhabditis elegans gene let-413 disrupt epithelial cell polarity and prevent the formation of cell junctions (Legouis et al., 20...

Transsynaptic Signaling by Postsynaptic Synapse-Associated Protein 97

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Human papillomaviruses, cervical cancer and cell polarity

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