FERM protein EPB41L5 is a novel member of the mammalian CRB–MPP5 polarity complex

Gosens, Ilse; Sessa, Alessandro; Hollander, Anneke I. den; Letteboer, Stef J.F.; Belloni, Valentina; Arends, Maarten; Bivic, André Le; Cremers, Frans P.M.; Broccoli, Vania; Roepman, Ronald

doi:10.1016/j.yexcr.2007.08.025

Cited by 62 publications

(68 citation statements)

References 49 publications

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“…The EPB4.1 protein family is involved in cellular morphogenesis, and EPB41L5 was particularly investigated in terms of apicobasal polarity establishment via interaction with CRUMBS in early development (35,36). Previous work demonstrated that EPB41L5 was required during early embryo gastrulation, which seemed to be partially a result of EPB41L5-dependent FA modulation and cell-cell contact establishment via cadherins (37).…”

Section: Discussionmentioning

confidence: 99%

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

Schell

Rogg

Suhm

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Podocytes form the outer part of the glomerular filter, where they have to withstand enormous transcapillary filtration forces driving glomerular filtration. Detachment of podocytes from the glomerular basement membrane precedes most glomerular diseases. However, little is known about the regulation of podocyte adhesion in vivo. Thus, we systematically screened for podocyte-specific focal adhesome (FA) components, using genetic reporter models in combination with iTRAQ-based mass spectrometry. This approach led to the identification of FERM domain protein EPB41L5 as a highly enriched podocyte-specific FA component in vivo. Genetic deletion of Epb41l5 resulted in severe proteinuria, detachment of podocytes, and development of focal segmental glomerulosclerosis. Remarkably, by binding and recruiting the RhoGEF ARGHEF18 to the leading edge, EPB41L5 directly controls actomyosin contractility and subsequent maturation of focal adhesions, cell spreading, and migration. Furthermore, EPB41L5 controls matrixdependent outside-in signaling by regulating the focal adhesome composition. Thus, by linking extracellular matrix sensing and signaling, focal adhesion maturation, and actomyosin activation EPB41L5 ensures the mechanical stability required for podocytes at the kidney filtration barrier. Finally, a diminution of EPB41L5-dependent signaling programs appears to be a common theme of podocyte disease, and therefore offers unexpected interventional therapeutic strategies to prevent podocyte loss and kidney disease progression.focal adhesion | actomyosin | podocyte | FSGS

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Section: Discussionmentioning

confidence: 99%

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

Schell

Rogg

Suhm

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…A characteristic phenotype of epb41l5-deficient embryos is the aberrant morphology of the hindbrain, which is associated with the failure of the organization of AJCs lining the putative ventricular surface and subsequent failure in brain ventricle inflation. These defects are believed to be associated with functions of Epb41l5 in limiting the distribution of Crb to the apical/ventricular surface of the neural tube (Hsu et al, 2006;Laprise et al, 2006;Gosens et al, 2007). These observations raised the possibility that the disorganization of the neuroepithelium and neural tube morphogenesis might contribute to the delays in delamination and differentiation of neurons in epb41l5-deficient embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that Epb41l5 interacts with the apical determinant Crb, restricts subcellular distribution of Crb to the ventricular surface of the neuroepithelium and organizes apico-basal polarity in neuroepithelium (Jensen et al, 2001;Jensen and Westerfield, 2004;Hsu et al, 2006;Laprise et al, 2006;Gosens et al, 2007). In zebrafish, epb41l5 was originally identified as mosaic eyes (moe) and Crb2a protein was more diffusely distributed in the neuroepithelium in moe b476 mutants (Hsu et al, 2006;Laprise et al, 2006) and in epb41l5-deficient embryos ( Fig.…”

Section: Mislocalization Of Neurons In Epb41l5-deficient Embryosmentioning

confidence: 92%

“…Epb41l5 belongs to a family of FERM proteins, which function as adaptors linking interacting cytoplasmic proteins to specific membrane compartments (Diakowski et al, 2006). Previous studies suggested diverse functions for Epb41l5 in the establishment of apical-basal polarity in neuroepithelial cells (Jensen et al, 2001;Jensen and Westerfield, 2004;Hsu et al, 2006;Laprise et al, 2006;Gosens et al, 2007), the promotion of epithelial-to-mesenchymal transition (EMT) (Lee et al, 2007;Hirano et al, 2008) and the regulation of apical membrane constriction of epithelial cells (Nakajima and Tanoue, 2010;Chu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Epb41l5 competes with Delta as a substrate for Mib1 to coordinate specification and differentiation of neurons

et al. 2016

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We identified Erythrocyte membrane protein band 4.1-like 5 (Epb41l5) as a substrate for the E3 ubiquitin ligase Mind bomb 1 (Mib1), which is essential for activation of Notch signaling. Although loss of Epb41l5 does not significantly alter the pattern of neural progenitor cells (NPCs) specified as neurons at the neural plate stage, it delays their delamination and differentiation after neurulation when NPCs normally acquire organized apical junctional complexes (AJCs) in the zebrafish hindbrain. Delays in differentiation are reduced by knocking down N-cadherin, a manipulation expected to help destabilize adherens junctions (AJs). This suggested that delays in neuronal differentiation in epb41l5-deficient embryos are related to a previously described role for Epb41l5 in facilitating disassembly of cadherindependent AJCs. Mib1 ubiquitylates Epb41l5 to promote its degradation. DeltaD can compete with Epb41l5 to reduce Mib1-dependent Epb41l5 degradation. In this context, increasing the number of NPCs specified to become neurons, i.e. cells expressing high levels of DeltaD, stabilizes Epb41l5 in the embryo. Together, these observations suggest that relatively high levels of Delta stabilize Epb41l5 in NPCs specified as neurons. This, we suggest, helps coordinate NPC specification with Epb41l5-dependent delamination and differentiation as neurons.

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“…This includes members of the apical Par proteins, namely Par-3 [formerly called ASIP (atypical PKC isotype-specific interacting protein) (Izumi et al, 1998)], Par-6α, Par-6β and Par-6γ, aPKCλ and aPKCζ (reviewed in Goldstein and Macara, 2007) and the Yurt orthologue YMO1 (EPB41L5; known as Mosaic eyes in zebrafish) (Gosens et al, 2007;Jensen and Westerfield, 2004). Most of these transiently interacting proteins are conserved not only in their domain organisation, but also in the nature of their interactions with other proteins in the Crumbs complex.…”

Section: Core and Transient Components Of The Crumbs Complex Are Consmentioning

confidence: 99%

The Crumbs complex: from epithelial-cell polarity to retinal degeneration

Bulgakova

Knust

2009

Journal of Cell Science

215

217

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The evolutionarily conserved Crumbs protein complex is a key regulator of cell polarity and cell shape in both invertebrates and vertebrates. The important role of this complex in normal cell function is illustrated by the finding that mutations in one of its components, Crumbs, are associated with retinal degeneration in humans, mice and flies. Recent results suggest that the Crumbs complex plays a role in the development of other disease processes that are based on epithelial dysfunction, such as tumorigenesis or the formation of cystic kidneys. Localisation of the complex is restricted to a distinct region of the apical plasma membrane that abuts the zonula adherens in epithelia and photoreceptor cells of invertebrates and vertebrates, including humans. In addition to the core components, a variety of other proteins can be recruited to the complex, depending on the cell type and/or developmental stage. Together with diverse post-transcriptional and posttranslational mechanisms that regulate the individual components, this provides an enormous functional diversity and flexibility of the complex. In this Commentary, we summarise findings concerning the organisation and modification of the Crumbs complex, and the conservation of its constituents from flies to mammals. In addition, we discuss recent results that suggest its participation in various human diseases, including blindness and tumour formation.

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FERM protein EPB41L5 is a novel member of the mammalian CRB–MPP5 polarity complex

Cited by 62 publications

References 49 publications

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

Epb41l5 competes with Delta as a substrate for Mib1 to coordinate specification and differentiation of neurons

The Crumbs complex: from epithelial-cell polarity to retinal degeneration

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