The LIM domain protein Wtip interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signalling

Wijk, Nicole Verhey van; Witte, Florian; Feike, Ann Carolin; Schambony, Alexandra; Birchmeier, Walter; Mundlos, Stefan; Stricker, Sigmar

doi:10.1016/j.bbrc.2009.09.086

Cited by 18 publications

(7 citation statements)

References 36 publications

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“…LIMD1 is implicated in osteoclast development through effects on transcription factor activity [35], but has also been reported to localise to focal adhesions [36]. WTIP interacts with and affects the transcriptional activity of Wilm's tumour protein, yet also localizes to cell-cell junctions and podocytes in kidney cells [37], and interacts with the receptor tyrosine kinase ROR2 [38]. LIMD1 and WTIP depletion induce distinct changes in actin organization: LIMD1 knockdown leads to an increase in peripheral F-actin bundles and stress fibres (in HeLa cells), whereas WTIP knockdown induces the formation of small F-actin-rich protrusions.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration

et al. 2011

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BackgroundCell migration is essential during development and in human disease progression including cancer. Most cell migration studies concentrate on known or predicted components of migration pathways.ResultsHere we use data from a genome-wide RNAi morphology screen in Drosophila melanogaster cells together with bioinformatics to identify 26 new regulators of morphology and cytoskeletal organization in human cells. These include genes previously implicated in a wide range of functions, from mental retardation, Down syndrome and Huntington's disease to RNA and DNA-binding genes. We classify these genes into seven groups according to phenotype and identify those that affect cell migration. We further characterize a subset of seven genes, FAM40A, FAM40B, ARC, FMNL3, FNBP3/FBP11, LIMD1 and ZRANB1, each of which has a different effect on cell shape, actin filament distribution and cell migration. Interestingly, in several instances closely related isoforms with a single Drosophila homologue have distinct phenotypes. For example, FAM40B depletion induces cell elongation and tail retraction defects, whereas FAM40A depletion reduces cell spreading.ConclusionsOur results identify multiple regulators of cell migration and cytoskeletal signalling that are highly conserved between Drosophila and humans, and show that closely related paralogues can have very different functions in these processes.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration

et al. 2011

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“…On the other hand, the effect of Wtip depletion on posterior cilia positioning suggests that, similar to Pk3, Wtip is involved in the establishment of PCP. Consistent with this possibility, Wtip binds Ror2, a known Wnt5a receptor implicated in morphogenesis and PCP 68 69 70 , and synergizes with Vangl2 to regulate spindle orientation in zebrafish embryos 58 71 . It remains to be investigated whether Wtip is directly involved in PCP.…”

Section: Discussionmentioning

confidence: 78%

Prickle3 synergizes with Wtip to regulate basal body organization and cilia growth

Chu

Ossipova

Ioannou

et al. 2016

Sci Rep

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PCP proteins maintain planar polarity in many epithelial tissues and have been implicated in cilia development in vertebrate embryos. In this study we examine Prickle3 (Pk3), a vertebrate homologue of Drosophila Prickle, in Xenopus gastrocoel roof plate (GRP). GRP is a tissue equivalent to the mouse node, in which cilia-generated flow promotes left-right patterning. We show that Pk3 is enriched at the basal body of GRP cells but is recruited by Vangl2 to anterior cell borders. Interference with Pk3 function disrupted the anterior polarization of endogenous Vangl2 and the posterior localization of cilia in GRP cells, demonstrating its role in PCP. Strikingly, in cells with reduced Pk3 activity, cilia growth was inhibited and γ-tubulin and Nedd1 no longer associated with the basal body, suggesting that Pk3 has a novel function in basal body organization. Mechanistically, this function of Pk3 may involve Wilms tumor protein 1-interacting protein (Wtip), which physically associates with and cooperates with Pk3 to regulate ciliogenesis. We propose that, in addition to cell polarity, PCP components control basal body organization and function.

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“…The nuclear export signal domain (NES), the SH3 binding domain (SH3), three LIM binding domains (LIM) and the PDZ binding domain (PDZ) are encoded by wtip. Recent studies suggest the following: (1) Wtip interacts with the C-terminus of the receptor tyrosine kinase Ror2 in yeast and mammalian cells (Verhey van Wijk et al, 2009), and (2) Ajuba LIM proteins (Ajuba, LIMD1 and WTIP) interact with Snail to remodel epithelia dynamics (Langer et al, 2008; Das Thakur et al, 2010). However, the subcellular localization of Wtip or its in vivo role during embryonic development is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Wtip and Vangl2 are required for mitotic spindle orientation and cloaca morphogenesis

et al. 2012

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SummaryDefects in cilia and basal bodies function are linked to ciliopathies, which result in kidney cyst formation. Recently, cell division defects have been observed in cystic kidneys, but the underlying mechanisms of such defects remain unclear. Wtip is an LIM domain protein of the Ajuba/Zyxin family, but its role in ciliogenesis during embryonic development has not been previously described. We report Wtip is enriched in the basal body and knockdown of wtip leads to pronephric cyst formation, cloaca malformation, hydrocephalus, body curvature, and pericardial edema. We additionally show that wtip knockdown embryos display segment-specific defects in the pronephros: mitotic spindle orientation defects are observed only in the anterior and middle pronephros; cloaca malformation is accompanied by a reduced number of ciliated cells; and ciliated cells lack the striated rootlet that originates from basal bodies, which results in a lack of cilia motility. Our data suggest that loss of Wtip function phenocopies Vangl2 loss of function, a core planar cell polarity (PCP) protein located in the basal body protein. Furthermore, we demonstrate that wtip and vangl2 interact genetically. Taken together, our results indicate that in zebrafish, Wtip is required for mitotic spindle orientation in the anterior and middle of the pronephros, cloaca morphogenesis, and PCP, which may underlie the molecular etiology of ciliopathies.

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The LIM domain protein Wtip interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signalling

Cited by 18 publications

References 36 publications

Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration

Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration

Prickle3 synergizes with Wtip to regulate basal body organization and cilia growth

Wtip and Vangl2 are required for mitotic spindle orientation and cloaca morphogenesis

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