KazrinE is a desmosome-associated liprin that colocalises with acetylated microtubules

Nachat, Rachida; Cipolat, Sara; Sevilla, Lisa M.; Chhatriwala, Mariya; Groot, Karen R.; Watt, Fiona M.

doi:10.1242/jcs.047266

Cited by 31 publications

(44 citation statements)

References 29 publications

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“…The nuclear presence of Kazrinin in vivo is in accordance with its nuclear localization in cell lines and human skin (supplementary material Fig. S1) (Nachat et al, 2009;Sevilla et al, 2008a). …”

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confidence: 69%

XenopusKazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity

Cho

Vaught

et al. 2010

Journal of Cell Science

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SummaryIn common with other p120-catenin subfamily members, Xenopus ARVCF (xARVCF) binds cadherin cytoplasmic domains to enhance cadherin metabolic stability or, when dissociated, modulates Rho-family GTPases. We report here that xARVCF binds and is stabilized by Xenopus KazrinA (xKazrinA), a widely expressed conserved protein that bears little homology to established protein families, and which is known to influence keratinocyte proliferation and differentiation and cytoskeletal activity. Although we found that xKazrinA binds directly to xARVCF, we did not resolve xKazrinA within a larger ternary complex with cadherin, nor did it co-precipitate with core desmosomal components. Instead, screening revealed that xKazrinA binds spectrin, suggesting a potential means by which xKazrinA localizes to cell-cell borders. This was supported by the resolution of a ternary biochemical complex of xARVCF-xKazrinA-x2-spectrin and, in vivo, by the finding that ectodermal shedding followed depletion of xKazrin in Xenopus embryos, a phenotype partially rescued with exogenous xARVCF. Cell shedding appeared to be the consequence of RhoA activation, and thereby altered actin organization and cadherin function. Indeed, we also revealed that xKazrinA binds p190B RhoGAP, which was likewise capable of rescuing Kazrin depletion. Finally, xKazrinA was found to associate with -catenins and p0071-catenins but not with p120-catenin, suggesting that Kazrin interacts selectively with additional members of the p120-catenin subfamily. Taken together, our study supports the essential role of Kazrin in development, and reveals the biochemical and functional association of KazrinA with ARVCF-catenin, spectrin and p190B RhoGAP. Journal of Cell Science FRMPD2 (Stenzel et al., 2009). In brief, the p120-subclass proteins exhibit both shared and non-overlapping interactions.To reveal novel ARVCF functions, we screened a Xenopus neurula (stage 18) cDNA library for proteins that interact with Xenopus laevis ARVCF (xARVCF) and identified Xenopus laevis Kazrin (xKazrinA). Biochemically, human KazrinA was previously shown to associate with the peripheral desmosomal proteins periplakin and envoplakin in human keratinocytes (Groot et al., 2004), with microtubules (isoformE) (Nachat et al., 2009), and to modulate RhoA (Sevilla et al., 2008a). We found that xKazrinA interacts directly with xARVCF but not with Xenopus laevis p120 (Xp120) or -catenin, and as reported earlier is present at cell-cell junctions (Groot et al., 2004). Surprisingly, we found that the xARVCF-xKazrinA complex associates and colocalizes with the spectrin cytoskeleton, rather than with cadherins at adherens junctions (Kaufmann et al., 2000;Mariner et al., 2000;Paulson et al., 2000), or with desmosomal core proteins (Groot et al., 2004). Our depletion of xKazrinA resulted in lessened embryonic tissue integrity (Sevilla et al., 2008b). In parallel, xARVCF protein levels were reduced and, supporting their functional interaction, exogenous xARVCF significantly rescued xKazrinA depletion phe...

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confidence: 69%

XenopusKazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity

Cho

Vaught

et al. 2010

Journal of Cell Science

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“…As all other members of the family, the widely expressed liprin-a1/PPFIA1 protein is made by an amino-terminal coiled-coil region and a carboxy-terminal region including three predicted steryl alpha motifs, which are present in several proteins to mediate interactions with either proteins, RNA or lipid membranes (Qiao and Bowie, 2005). Liprins show some degree of homology with kazrinE, a widely expressed cytoplasmic protein with three carboxy-terminal steryl alpha motifs that is involved in epidermal differentiation (Nachat et al, 2009). Liprin-a proteins may interact with different ligands, including liprin-b, the tyrosine phosphatase receptor LAR, kinesin motor proteins, the ArfGAP GIT1 and the adaptor proteins ERC and CASK (see de Curtis, 2011 for a review).…”

Section: Introductionmentioning

confidence: 99%

Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation

et al. 2010

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Migration of cells and degradation of the extracellular matrix (ECM) are required for efficient tumor cell invasion, but the underlying molecular mechanisms are only partially known. The PPFIA1 gene for liprin-a1 is frequently amplified in human breast cancers. We recently demonstrated that liprin-a1 is an important regulator of cell edge dynamics during motility. We show, herein, that the liprin-a1 protein is highly expressed in human breast tumors. Functional analysis shows that liprin-a1 is specifically required for the migration and invasion of highly invasive human breast cancer MDA-MB-231 cells. We used time-lapse analysis to demonstrate defects in the motility of liprin-a1-depleted cells that include a striking instability of the lamellipodia. Liprin-a1 levels altered by either RNA interference or overexpression affected also cell spreading and the number of invadopodia per cell, but not the density of invadopodia per unit of surface area. On the other hand, silencing of liprin-a1 inhibited the degradation of the ECM, whereas its overexpression enhanced degradation, resulting in significant negative or positive effects, respectively, on the area of degradation per invadopodium. Transfection of fluorescent-labeled cortactin revealed that depletion of liprin-a1 also affected the assembly and disassembly of invadopodia, with decrease of their lifetime. Our results strongly support a novel important role of liprin-a1 in the regulation of human tumor cell invasion.

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“…ARVCF-catenin appears to bind the novel (scaffolding?) protein Kazrin (K. Cho, T. Vaught, J. M. Jennings, M. Kloc, D.G., C. Papasakelariou, H. Ji, A. P. Kowalczyk and P.D.M., unpublished results), which shuttles in and out of the nucleus when not at junctional regions or associated with microtubules (Groot et al, 2004;Nachat et al, 2009;Sevilla et al, 2008). d-catenin associates with Kaiso (Rodova et al, 2004), possibly sharing gene targets with p120.…”

Section: Other Nuclear Roles?mentioning

confidence: 99%

The catenin family at a glance

McCrea

2010

Journal of Cell Science

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KazrinE is a desmosome-associated liprin that colocalises with acetylated microtubules

Cited by 31 publications

References 29 publications

XenopusKazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity

XenopusKazrin interacts with ARVCF-catenin, spectrin and p190B RhoGAP, and modulates RhoA activity and epithelial integrity

Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation

The catenin family at a glance

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