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Varicose: a MAGUK required for the maturation and function of Drosophila septate junctions.

ABSTRACT: BACKGROUND:Scaffolding proteins belonging to the membrane associated guanylate kinase (MAGUK) superfamily function as adapters linking cytoplasmic and cell surface proteins to the cytoskeleton to regulate cell-cell adhesion, cell-cell communication and signal transduction. We characterize here a Drosophila MAGUK member, Varicose (Vari), the homologue of vertebrate scaffolding protein PALS2. RESULTS:Varicose localizes to pleated septate junctions (pSJs) of all embryonic, ectodermally-derived epithelia and peripheral glia. In vari mutants, essential SJ proteins NeurexinIV and FasciclinIII are mislocalized basally and epithelia develop a leaky paracellular seal. In addition, vari mutants display irregular tracheal tube diameters and have reduced lumenal protein accumulation, suggesting involvement in tracheal morphogenesis. We found that Vari is distributed in the cytoplasm of the optic lobe neuroepithelium, as well as in a subset of neuroblasts and differentiated neurons of the nervous system. We reduced vari function during the development of adult epithelia with a partial rescue, RNA interference and generation of genetically mosaic tissue. All three approaches demonstrate that vari is required for the patterning and morphogenesis of adult epithelial hairs and bristles. CONCLUSION:Varicose is involved in scaffold assembly at the SJ and has a role in patterning and morphogenesis of adult epithelia.

SUBMITTER: Moyer KE

PROVIDER: S-EPMC2575209 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Varicose: a MAGUK required for the maturation and function of Drosophila septate junctions.

Moyer Katherine E KE Jacobs J Roger JR

BMC developmental biology 20081010

<h4>Background</h4>Scaffolding proteins belonging to the membrane associated guanylate kinase (MAGUK) superfamily function as adapters linking cytoplasmic and cell surface proteins to the cytoskeleton to regulate cell-cell adhesion, cell-cell communication and signal transduction. We characterize here a Drosophila MAGUK member, Varicose (Vari), the homologue of vertebrate scaffolding protein PALS2.<h4>Results</h4>Varicose localizes to pleated septate junctions (pSJs) of all embryonic, ectodermal ...[more]

PMID: 18847477

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Project description:BackgroundA complex of three cell adhesion molecules (CAMs) Neurexin IV(Nrx IV), Contactin (Cont) and Neuroglian (Nrg) is implicated in the formation of septate junctions between epithelial cells in Drosophila. These CAMs are interdependent for their localization at septate junctions and e.g. null mutation of nrx IV or cont induces the mislocalization of Nrg to the baso-lateral membrane. These mutations also result in ultrastructural alteration of the strands of septate junctions and breakdown of the paracellular barrier. Varicose (Vari) and Coracle (Cora), that both interact with the cytoplasmic tail of Nrx IV, are scaffolding molecules required for the formation of septate junctions.ResultsWe conducted photobleaching experiments on whole living Drosophila embryos to analyze the membrane mobility of CAMs at septate junctions between epithelial cells. We show that GFP-tagged Nrg and Nrx IV molecules exhibit very stable association with septate junctions in wild-type embryos. Nrg-GFP is mislocalized to the baso-lateral membrane in nrx IV or cont null mutant embryos, and displays increased mobile fraction. Similarly, Nrx IV-GFP becomes distributed to the baso-lateral membrane in null mutants of vari and cora, and its mobile fraction is strongly increased. The loss of Vari, a MAGUK protein that interacts with the cytoplasmic tail of Nrx IV, has a stronger effect than the null mutation of nrx IV on the lateral mobility of Nrg-GFP.ConclusionThe strands of septate junctions display a stable behavior in vivo that may be correlated with their role of paracellular barrier. The membrane mobility of CAMs is strongly limited when they take part to the multimolecular complex forming septate junctions. This restricted lateral diffusion of CAMs depends on both adhesive interactions and clustering by scaffolding molecules. The lateral mobility of CAMs is strongly increased in embryos presenting alteration of septate junctions. The stronger effect of vari by comparison with nrx IV null mutation supports the hypothesis that this scaffolding molecule may cross-link different types of CAMs and play a crucial role in stabilizing the strands of septate junctions.

Dataset Information

Varicose: a MAGUK required for the maturation and function of Drosophila septate junctions.

Publications

Varicose: a MAGUK required for the maturation and function of Drosophila septate junctions.

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