CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity

Lozovatsky, Larissa; Abayasekara, Nirmalee; Piawah, Sorbarikor; Walther, Zenta

doi:10.1091/mbc.e09-04-0280

Cited by 27 publications

(16 citation statements)

References 58 publications

(73 reference statements)

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“…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).…”

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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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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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“…Future studies will elucidate the requirements for membrane recruitment of Lin7. In the mouse intestinal epithelium, Lin7C is associated with the baso-lateral membrane, a process that depends on CASK (calcium/calmodulin-dependent serine protein kinase), a scaffolding protein of the MAGUK family (Lozovatsky et al, 2009). Similarly, Lin-7C localization at the baso-lateral surface of Madine Darbine Canine Kidney (MDCK) cells and in renal epithelia requires its interaction with CASK (Straight et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Fluorescently tagged Lin7c is a dynamic marker for polarity maturation in the zebrafish retinal epithelium

Luz

Knust

2013

Biology Open

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SummaryDevelopment of epithelial cell polarity is a highly dynamic process, and often established by the sequential recruitment of conserved protein complexes, such as the Par or the Crumbs (Crb) complex. However, detailed insights into the refinement of polarity and the formation of the complexes are still lacking. Here, we established fluorescently tagged Lin7c, a core member of the Crb complex, as an ideal tool to follow development of polarity in zebrafish epithelia. We find that in gastrula stages, RFP-Lin7c is found in the cytosol of the enveloping layer, while Pard3-GFP is already polarized at this stage. During development of the retinal epithelium, RFP-Lin7c localization is refined from being cytosolic at 14 hours post fertilization (hpf) to almost entirely apical in cells of the eye cup at 28 hpf. This apical Lin7c localization depends on the Crb complex members Oko meduzy and Nagie oko. Thus, fluorescently tagged Lin7c can be used in a broad range of epithelia to follow polarity maturation in vivo and specifically to elucidate the sequence of events determining Crb complex-mediated polarity.

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“…Dlg1 has not been reported to bind directly to cell membranes, and does not contain a membrane localisation domain; instead another factor must be involved in its recruitment to the membrane. It has been reported that the MAGUK protein CASK is involved in Dlg1 localisation to the plasma membrane in some tissues [14,15]. CASK is a multi-domain scaffolding protein with unusual magnesium-independent kinase activity [16], and contains a Hook domain, which mediates interaction with the cytoskeleton and allows for membrane binding [14].…”

Section: Cask Is Required For Dlg1 Membrane Localisation Lumen Formamentioning

confidence: 99%

The interaction between the tumour suppressor Dlg1 and the MAGUK protein CASK is required for oriented cell division in mammalian epithelia

Porter

White

Mack

et al. 2018

Preprint

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Oriented cell divisions are important for the formation of normal epithelial structures. Dlg1, a tumour suppressor, is required for oriented cell division in Drosophila epithelia and chick neuroepithelia, but how Dlg1 is localised to the membrane and its importance in mammalian epithelia are unknown. Here we show that Dlg1 is required in non-transformed mammalian epithelial cells for oriented cell divisions, and for normal lumen formation in 3D culture. We demonstrate that CASK, a membrane-associated scaffold, is the factor responsible for Dlg1 membrane localisation during spindle orientation, and thereby identify a new cellular function for CASK. We show that depletion of CASK leads to misoriented divisions in 3D, and to the formation of multilumen structures in cultured kidney and breast epithelial cells. Blocking the direct interaction between CASK and Dlg1 with an interfering peptide disrupts spindle orientation and causes multilumen formation. We further show that the Dlg1-CASK interaction is important for the membrane localisation of the canonical LGN-NuMA complex, required for attachment of the mitotic spindle to the membrane and its correct positioning, as well as for astral microtubule stability. Together these results establish the importance of the CASK-Dlg1 interaction in oriented cell division and epithelial integrity.

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CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity

Cited by 27 publications

References 58 publications

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

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

Fluorescently tagged Lin7c is a dynamic marker for polarity maturation in the zebrafish retinal epithelium

The interaction between the tumour suppressor Dlg1 and the MAGUK protein CASK is required for oriented cell division in mammalian epithelia

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