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

Moyer, Katherine; Jacobs, J. Roger

doi:10.1186/1471-213x-8-99

Cited by 35 publications

(38 citation statements)

References 69 publications

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“…To do so, we tested whether depletion of Varicose, a MAGUK protein required for septate junction assembly and function (Bachmann et al, 2008; Moyer and Jacobs, 2008; Wu et al, 2007), was able to suppress the wheezy tube dilation defect. We found that transition zone tube dilation was completely suppressed in 52% of terminal cells and partially suppressed in another 20%, while an additional 9% of cells actually showed the discontinuous tube (“gap”) defect characteristic of lotus (n=48) (Figure 6F).…”

Section: Resultsmentioning

confidence: 99%

Focal Defects in Single-Celled Tubes Mutant for Cerebral Cavernous Malformation 3, GCKIII, or NSF2

2013

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Tubes of differing cellular architecture connect into networks. In the Drosophila tracheal system, two tube types connect within single cells (terminal cells); however, the genes that mediate this interconnection are unknown. Here we characterize two genes that are essential for this process: lotus, required for maintaining a connection between the tubes, and wheezy, required to prevent local tube dilation. We find that lotus encodes N-ethylmaleimide Sensitive Factor 2 (NSF2), while wheezy encodes Germinal Center Kinase III (GCKIII). GCKIIIs are effectors of Cerebral Cavernous Malformation 3 (CCM3), a protein mutated in vascular disease. Depletion of CCM3 by RNA interference phenocopies wheezy; thus, CCM3 and GCKIII, which prevent capillary dilation in humans, prevent tube dilation in Drosophila trachea. Ectopic junctional and apical proteins are present in wheezy terminal cells, and we show that tube dilation is suppressed by reduction of NSF2, of the apical determinant Crumbs, or of septate junction protein Varicose.

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Section: Resultsmentioning

confidence: 99%

Focal Defects in Single-Celled Tubes Mutant for Cerebral Cavernous Malformation 3, GCKIII, or NSF2

2013

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“…The requirement of MPP6 was reported for the maturation and function of Drosophila septate junctions (20). In addition, other MAGUKs, such as Dlg1 (5,6,8,13) and MPP5 (25), were reported to affect myelination if they were deficient due to the disruption of the phosphatidylinositol metabolism with Mtmr-2 (myotubularin-related 2) and PTEN (phosphatase and tensin homolog).…”

Section: Discussionmentioning

confidence: 99%

Essential Function of Protein 4.1G in Targeting of Membrane Protein Palmitoylated 6 into Schmidt-Lanterman Incisures in Myelinated Nerves

Terada

Saitoh

Ohno

et al. 2012

Molecular and Cellular Biology

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Protein 4.1G is a membrane skeletal protein found in specific subcellular structures in myelinated Schwann cells and seminiferous tubules. Here, we show that in the mouse sciatic nerve, protein 4.1G colocalized at Schmidt-Lanterman incisures (SLI) and the paranodes with a member of the membrane-associated guanylate kinase (MAGUK) family, membrane protein palmitoylated 6 (MPP6). Coimmunoprecipitation experiments revealed that MPP6 was interacting with protein 4.1G. In contrast to wild-type nerves, in 4.1G knockout mice, MPP6 was found largely in the cytoplasm near Schwann cell nuclei, indicating an abnormal protein transport. Although the SLI remained in the 4.1G knockout sciatic nerves, as confirmed by E-cadherin immunostaining, their shape was altered in aged 4.1G knockout nerves compared to their shape in wild-type nerves. In the seminiferous tubules, MPP6 was localized similarly to protein 4.1G along cell membranes of the spermatogonium and early spermatocytes. However, in contrast to myelinated peripheral nerves, the specific localization of MPP6 in the seminiferous tubules was unaltered in the absence of protein 4.1G. These results indicate that 4.1G has a specific role in the targeting of MPP6 to the SLI and the assembly of these subcellular structures. P rotein 4.1G (4.1G) is a member of the 4.1 family (27, 46), a group of membrane skeletal proteins that link various components to the spectrin-actin network (10). We have previously reported that 4.1G is present in rodent Schwann cells (7, 24) and mouse seminiferous tubules (40, 41). In peripheral nerves, 4.1G is found at the Schmidt-Lanterman incisures (SLI) and the paranodal loops of myelinated Schwann cells (24). The SLI are funnelshaped interruptions within the myelin sheath of nerve fibers. They contain high concentrations of actin and spectrin (35, 42), which forms a membrane skeleton that might contribute to the elasticity and stability of these structures.Membrane-associated guanylate kinase (MAGUK) family proteins contain PDZ (for postsynaptic density 95 [PSD-95]/Drosophila disks large [Dlg]/zonula occludens 1 [ZO-1]), GUK (guanylate kinase), and SH3 (src homology 3) domains, and they localize to specific domains at the plasma membranes (9, 11). In epithelial cells, for example, some MAGUKs, such as Dlg and ZO-1, are required for the formation of adherens and tight junctions, respectively. In addition to their function as membrane scaffolds (16, 21), several MAGUKs also control intracellular protein transport through their ability to bind motor proteins (45, 49). Interestingly, some MAGUKs contain specific domains that interact with 4.1 proteins (14,17,18). In the current study, we report the identification of membrane protein palmitoylated 6 (MPP6) (also known as PALS2, VAM1, and p55T [http://www .genenames.org/]) as a novel MAGUK molecule that interacts with 4.1G in peripheral nerves. We further demonstrate that the interaction between 4.1G and MPP6 is essential for the targeting of the latter into SLI. MATERIALS AND METHODS Animals and anesthes...

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“…Mutations disrupting chitin biosynthesis ( krotzkopf verkehrt and mummy/cystic ) and matrix assembly ( knickkopf and retroactive ) grow over-dilated tubes (Araujo, et al 2005; Devine, et al 2005; Moussian, et al 2006). In contrast, mutations affecting chitin modification ( vermiform and serpentine ) (Luschnig, et al 2006) and septate junctions (SJ, analogous to vertebrate tight junctions) lead to longer tubes (Behr, et al 2003; Paul, et al 2003; Llimargas, et al 2004; Wu, et al 2004; Luschnig, et al 2006; Moyer and Jacobs. 2008; Laprise, et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size

Iordanou

Chandran

Yang

et al. 2014

Developmental Biology

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Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes. Cysts in unicellular tubes are enlargements of the apical lumen, whereas cysts in intracellular tubes are cytoplasmic vacuole-like compartments. The cyst phenotype in expansion mutants is similar to, but weaker than, that observed in double mutants of Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E and Ptp10D negatively regulate the receptor tyrosine kinase (RTK) pathways, especially epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor/breathless (FGFR, Btl) signaling to maintain the proper size of unicellular and intracellular tubes. We show Exp genetically interacts with RTK signaling, the downstream targets of RPTPs. Cyst size and number in expansion mutants is enhanced by increased RTK signaling and suppressed by reduced RTK signaling. Genetic interaction studies strongly suggest that Exp negatively regulates RTK (EGFR, Btl) signaling to ensure proper tube sizes. Smad proteins generally function as intermediate components of the transforming growth factor-β (TGF-β, DPP) signaling pathway. However, no obvious genetic interaction between expansion and TGF-β (DPP) signaling was observed. Therefore, Expansion does not function as a typical Smad protein. The expansion phenotype demonstrates a novel role for Smad-like proteins in epithelial tube formation.

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

Cited by 35 publications

References 69 publications

Focal Defects in Single-Celled Tubes Mutant for Cerebral Cavernous Malformation 3, GCKIII, or NSF2

Focal Defects in Single-Celled Tubes Mutant for Cerebral Cavernous Malformation 3, GCKIII, or NSF2

Essential Function of Protein 4.1G in Targeting of Membrane Protein Palmitoylated 6 into Schmidt-Lanterman Incisures in Myelinated Nerves

The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size

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