Disease relevance of Vang

• Reductions in CBP activity are the underlying cause of Rubinstein-Taybi syndrome, which is, in part, characterized by several eye defects, including strabismus, cataracts, juvenile glaucoma, and coloboma of the eyelid, iris, and lens [1].

High impact information on Vang

• Here we show that a mutation in Vangl2, a mammalian homologue of the Drosophila PCP gene Strabismus/Van Gogh, results in significant disruptions in the polarization of stereociliary bundles in mouse cochlea as a result of defects in the direction of movement and/or anchoring of the kinocilium within each hair cell [2].
• Here we show that this important process depends on a functional complex formed between the tumour suppressor and adaptor protein Discs-Large (Dlg) and the integral membrane protein Strabismus (Stbm)/Van Gogh (Vang) [3].
• Conversely, overexpression of Dlg and Stbm synergistically induced excessive plasma membrane formation [3].
• These findings suggest that the Dlg-Stbm complex recruits membrane-associated proteins and lipids from internal membranes to sites of new plasma membrane formation [3].
• In regard to cell behaviour, both gain-of-function and loss-of-function assays reveal a role for Stbm in mediating cell movements during gastrulation [4].

Biological context of Vang

• Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling [5].
• At prophase, Stbm promotes the anterior localization of Pins [6].
• We report the enhancement of the strabismus tissue polarity phenotype by mutations in two other tissue polarity genes, flamingo and prickle [7].
• We propose Trilobite/Stbm mediates cellular interactions that confer directionality on distinct movements during vertebrate embryogenesis [8].
• On the wing, Van Gogh mutations cause an altered polarity pattern that is typical of mutations that inactivate the frizzled signaling/signal transduction pathway [9].

Anatomical context of Vang

• We show that Strabismus binds directly to Dishevelled and Prickle and is able to recruit them to membranes [10].
• We demonstrate that in the zebrafish gastrula, Fmi1 proteins function in concert with each other and with the vertebrate PCP proteins, Wnt11 and Strabismus, to mediate convergence and extension during gastrulation, without altering early dorso-ventral patterning [11].
• It has been suggested that this polarity might be controlled by genes homologous to those that control planar cell polarity (PCP) in Drosophila, and vertebrate homologues of the Drosophila PCP genes Van Gogh/strabismus and flamingo/starry night are indeed essential for normal hair cell PCP [12].

Physical interactions of Vang

• Thus our data suggest that the Stbm/Pk complex modulates Fz/Dsh activity, resulting in a symmetry-breaking step during polarity signaling [5].
• PCP is induced in Drosophila by the asymmetrical localization of Frizzled-Dishevelled-Diego-Starry night (Flamingo) complex and Van Gogh (Strabismus)-Prickle complex [13].

Regulatory relationships of Vang

• The planar cell polarity protein Strabismus promotes Pins anterior localization during asymmetric division of sensory organ precursor cells in Drosophila [6].
• While neither of these proteins is required for the other's localization, Prickle localization is influenced by Strabismus function [7].

Other interactions of Vang

• Through this interaction, Pk affects Stbm membrane localization and can cause clustering of Stbm [5].
• We propose that the Stbm-dependent recruitment of Pins at the anterior cortex of the pI cell is a novel read-out of planar cell polarity [6].
• Flamingo and Strabismus co-localize for several rows posterior to the morphogenetic furrow and subsequently diverge [7].
• In the absence of strabismus activity, the planar polarity proteins Dishevelled and Prickle are mislocalised in the cell [10].
• Unlike these proteins, however, Stbm has little effect on conventional Wnt/beta-catenin signaling in either frog or fly assays [14].

References