Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Albinism ocular type 1 (OA1) is an X-linked type of albinism that mainly effects pigment production in the eye, resulting in hypopigmentation of the retina, nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers, and reduced visual acuity. The OA1 gene is located on chromosome Xp22.32 and the coding sequence is divided into nine exons. The protein is an integral transmembrane protein that has weak similarities to G protein-coupled receptors. A total of 25 missense, two nonsense, nine frameshift, and five splicing mutations have been reported in the OA1 gene associated with OA1. There are also several deletions of some or all exons of the OA1 gene with deletions of exon 2 resulting from unequal crossing-over, due to flanking Alu repeats. Mutation and polymorphism data on this gene is available from the International Albinism Center - Albinism Database web site (http://www.cbc.umn.edu/tad).
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PMID:New insights into ocular albinism type 1 (OA1): Mutations and polymorphisms of the OA1 gene. 1179 67

WNT signaling pathway is implicated in carcinogenesis and embryogenesis. WNT signal is transduced to the beta-catenin - TCF pathway, the JNK pathway, or the Ca2+-releasing pathway through seven-transmembrane-type WNT receptors encoded by Frizzled (FZD) genes. Xenopus Strabismus (Stbm) is a tetra-spanning transmembrane protein interacting with Dishevelled, and is a negative regulator of the WNT - beta-catenin - TCF signaling pathway. STB1/KIAA1215/VANGL2 is a human orthologue of Xenopus Stbm (90.6% total-amino-acid identity). Here, STB2/VANGL1 gene fragments were identified in human genome draft sequences by using bioinformatics, and STB2 cDNAs were isolated by using cDNA-PCR. STB2 gene consisted of at lest 7 exons, and encoded a 524-amino-acid protein with 4 transmembrane domains and the C-terminal Ser/Thr-X-Val motif. Human STB2 was homologous to human STB1 (73.1% total-amino-acid identity) and Xenopus Stbm (72.7% total-amino-acid identity). STB2 gene was clustered with Calsequestrin 2 (CASQ2) gene in tail-to-tail manner (interval less than 5.0 kb), and CASQ2 gene is mapped to human chromosome 1p11-p13.3 or linked to human chromosome 1p13-p21. STB2 mRNAs of 4.8- and 6.8-kb in size were expressed almost ubiquitously in various normal tissues. STB2 mRNA was significantly up-regulated in gastric cancer cell lines MKN28, MKN74, pancreatic cancer cell lines BxPC-3, PSN-1 and Hs766T. On the other hand, STB2 mRNA was significantly down-regulated in a pancreatic cancer cell line AsPC-1. This is the first report on molecular cloning and characterization of STB2.
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PMID:Molecular cloning and characterization of Strabismus 2 (STB2). 1195 95

Embryonic morphogenesis is driven by a suite of cell behaviours, including coordinated shape changes, cellular rearrangements and individual cell migrations, whose molecular determinants are largely unknown. In the zebrafish, Dani rerio, trilobite mutant embryos have defects in gastrulation movements and posterior migration of hindbrain neurons. Here, we have used positional cloning to demonstrate that trilobite mutations disrupt the transmembrane protein Strabismus (Stbm)/Van Gogh (Vang), previously associated with planar cell polarity (PCP) in Drosophila melanogaster, and PCP and canonical Wnt/beta-catenin signalling in vertebrates. Our genetic and molecular analyses argue that during gastrulation, trilobite interacts with the PCP pathway without affecting canonical Wnt signalling. Furthermore, trilobite may regulate neuronal migration independently of PCP molecules. We show that trilobite mediates polarization of distinct movement behaviours. During gastrulation convergence and extension movements, trilobite regulates mediolateral cell polarity underlying effective intercalation and directed dorsal migration at increasing velocities. In the hindbrain, trilobite controls effective migration of branchiomotor neurons towards posterior rhombomeres. Mosaic analyses show trilobite functions cell-autonomously and non-autonomously in gastrulae and the hindbrain. We propose Trilobite/Stbm mediates cellular interactions that confer directionality on distinct movements during vertebrate embryogenesis.
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PMID:Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. 1210 18

In addition to the apical-basal polarity pathway operating in epithelial cells, a planar cell polarity (PCP) pathway establishes polarity within the plane of epithelial tissues and is conserved from Drosophila to mammals. In Drosophila, a 'core' group of PCP genes including frizzled (fz), flamingo/starry night, dishevelled (dsh), Van Gogh/strabismus and prickle, function to regulate wing hair, bristle and ommatidial polarity. In vertebrates, the PCP pathway regulates convergent extension movements and neural tube closure, as well as the orientation of stereociliary bundles of sensory hair cells in the inner ear. Here we show that a mutation in the mouse protein tyrosine kinase 7 (PTK7) gene, which encodes an evolutionarily conserved transmembrane protein with tyrosine kinase homology, disrupts neural tube closure and stereociliary bundle orientation, and shows genetic interactions with a mutation in the mouse Van Gogh homologue vangl2. We also show that PTK7 is dynamically localized during hair cell polarization, and that the Xenopus homologue of PTK7 is required for neural convergent extension and neural tube closure. These results identify PTK7 as a novel regulator of PCP in vertebrates.
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PMID:PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. 1522 3

The Frizzled (Fz) receptor is required cell autonomously in Wnt/beta-catenin and planar cell polarity (PCP) signaling. In addition to these requirements, Fz acts nonautonomously during PCP establishment: wild-type cells surrounding fz(-) patches reorient toward the fz(-) cells. The molecular mechanism(s) of nonautonomous Fz signaling are unknown. Our in vivo studies identify the extracellular domain (ECD) of Fz, in particular its CRD (cysteine rich domain), as critical for nonautonomous Fz-PCP activity. Importantly, we demonstrate biochemical and physical interactions between the FzECD and the transmembrane protein Van Gogh/Strabismus (Vang/Stbm). We show that this function precedes cell-autonomous interactions and visible asymmetric PCP factor localization. Our data suggest that Vang/Stbm can act as a FzECD receptor, allowing cells to sense Fz activity/levels of their neighbors. Thus, direct Fz-Vang/Stbm interactions represent an intriguing mechanism that may account for the global orientation of cells within the plane of their epithelial field.
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PMID:The frizzled extracellular domain is a ligand for Van Gogh/Stbm during nonautonomous planar cell polarity signaling. 1880 40

The coordinated polarization of cells in the plane of a tissue, termed planar polarity, is a characteristic feature of epithelial tissues [1]. In the fly wing, trichome positioning is dependent on the core planar polarity proteins adopting asymmetric subcellular localizations at apical junctions, where they form intercellular complexes that link neighboring cells [1-3]. Specifically, the seven-pass transmembrane protein Frizzled and the cytoplasmic proteins Dishevelled and Diego localize to distal cell ends, the four-pass transmembrane protein Strabismus and the cytoplasmic protein Prickle localize proximally, and the seven-pass transmembrane spanning atypical cadherin Flamingo localizes both proximally and distally. To establish asymmetry, these core proteins are sorted from an initially uniform distribution; however, the mechanisms underlying this polarized trafficking remain poorly understood. Here, we describe the identification of retromer, a master controller of endosomal recycling [4-6], as a key component regulating core planar polarity protein localization in Drosophila. Through generation of mutants, we verify that loss of the retromer-associated Snx27 cargo adaptor, but notably not components of the Wash complex, reduces junctional levels of the core proteins Flamingo and Strabismus in the developing wing. We establish that Snx27 directly associates with Flamingo via its C-terminal PDZ binding motif, and we show that Snx27 is essential for normal Flamingo trafficking. We conclude that Wash-independent retromer function and the Snx27 cargo adaptor are important components in the endosomal recycling of Flamingo and Strabismus back to the plasma membrane and thus contribute to the establishment and maintenance of planar polarization.
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PMID:Retromer Controls Planar Polarity Protein Levels and Asymmetric Localization at Intercellular Junctions. 3066

Planar polarity refers to cellular polarity in an orthogonal plane to apicobasal polarity, and is seen across scales from molecular distributions of proteins to tissue patterning. In many contexts it is regulated by the evolutionarily conserved 'core' planar polarity pathway that is essential for normal organismal development. Core planar polarity pathway components form asymmetric intercellular complexes that communicate polarity between neighbouring cells and direct polarised cell behaviours and the formation of polarised structures. The core planar polarity pathway consists of six structurally different proteins. In the fruitfly Drosophila melanogaster, where the pathway is best characterised, an intercellular homodimer of the seven-pass transmembrane protein Flamingo interacts on one side of the cell junction with the seven-pass transmembrane protein Frizzled, and on the other side with the four-pass transmembrane protein Strabismus. The cytoplasmic proteins Diego and Dishevelled are co-localised with Frizzled, and Prickle co-localises with Strabismus. Between these six components there are myriad possible molecular interactions, which could stabilise or destabilise the intercellular complexes and lead to their sorting into polarised distributions within cells. Post-translational modifications are key regulators of molecular interactions between proteins. Several post-translational modifications of core proteins have been reported to be of functional significance, in particular phosphorylation and ubiquitination. In this review, we discuss the molecular control of planar polarity and the molecular ecology of the core planar polarity intercellular complexes. Furthermore, we highlight the importance of understanding the spatial control of post-translational modifications in the establishment of planar polarity.
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PMID:Molecular mechanisms mediating asymmetric subcellular localisation of the core planar polarity pathway proteins. 3282 Jul 99