Polarized Transport of Frizzled along the Planar Microtubule Arrays in Drosophila Wing Epithelium

Shimada, Yuko; Yonemura, Shigenobu; Ohkura, Hiroyuki; Strutt, David; Uemura, Tadashi

doi:10.1016/j.devcel.2005.11.016

Cited by 272 publications

(349 citation statements)

References 69 publications

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“…A critical determinant of normal bristle and hair polarity in cells of the Drosophila wing is the proper localization of Fz and Dsh to the distal end of the cells, and vesicles have been shown to transport both of these proteins along MTs (15,16). Because pk pk homozygous mutants show altered bristle/hair polarity in the wing (5, 7), which would be predicted if Fz/Dsh vesicles were not properly transported distally, we reasoned that Pk pk might be involved in directly influencing transport of the Fz/Dshcontaining vesicles in the wing cells and that perhaps similar mechanisms might underlie vesicle transport in neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Shimada and colleagues (15) previously reported that in wing cells Fz is transported in vesicles toward the plus ends of MTs, eventually accumulating at the distal ends of the cells. pk pk mutants show disruptions in hair and bristle polarity in the wing (5, 7), and recent evidence (16) shows that prickle influences vesicle transport in wing cells in a manner similar to what we have observed in neurons.…”

Section: Discussionmentioning

confidence: 99%

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prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies

Ehaideb

Iyengar

Ueda³

et al. 2014

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

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Recent analyses in flies, mice, zebrafish, and humans showed that mutations in prickle orthologs result in epileptic phenotypes, although the mechanism responsible for generating the seizures was unknown. Here, we show that Prickle organizes microtubule polarity and affects their growth dynamics in axons of Drosophila neurons, which in turn influences both anterograde and retrograde vesicle transport. We also show that enhancement of the anterograde transport mechanism is the cause of the seizure phenotype in flies, which can be suppressed by reducing the level of either of two Kinesin motor proteins responsible for anterograde vesicle transport. Additionally, we show that seizure-prone prickle mutant flies have electrophysiological defects similar to other fly mutants used to study seizures, and that merely altering the balance of the two adult prickle isoforms in neurons can predispose flies to seizures. These data reveal a previously unidentified pathway in the pathophysiology of seizure disorders and provide evidence for a more generalized cellular mechanism whereby Prickle mediates polarity by influencing microtubule-mediated transport.epilepsy | planar cell polarity | spiny-legs | EB1-GFP | neurodegeneration E pilepsy, which affects ∼1% of the population, is a disabling and debilitating disease characterized by recurrent seizures. Coupling genetic analysis of human epilepsy cases with functional validation in animal models, we previously showed that mutations in human PRICKLE1 and PRICKLE2, as well as mutations in mouse, zebrafish and fly prickle (pk) orthologs, increase susceptibility to seizures (1-3). We recently showed that both mouse and fly Prickle can associate with Synapsin (4). However, little is known regarding what cellular process connects Prickle with epilepsy. Products of the prickle gene work in concert with a group of cytoplasmic and membrane-associated proteins including Frizzled (Fz) and Dishevelled (Dsh) to establish polarity of structures such as hairs and bristles in the fly epidermis (5-8). The fly pk locus expresses three alternately spliced isoforms, two of which, pk sple (prickle-spiny-legs) and pk pk (prickle-prickle), are expressed in postembryonic animals (5, 7). Homozygous pk pk and pk sple fly mutants show strong planar cell polarity (PCP) phenotypes in the wing and in the legs, respectively, in addition to other regions of the adult body (6, 7). Prickle (Pk) protein isoforms are localized to the proximal end of fly wing cells, whereas Fz and Dsh are localized distally (8).Here, we show that vesicle transport dynamics are altered in neurons of Drosophila mutant for either adult isoform of prickle. Seizure-prone pk sple heterozygotes show enhanced vesicle transport (along with electrophysiological defects similar to other seizure-prone mutant flies), and the seizure phenotypes can be rescued by lowering the dose of vesicle transport motor proteins. However, pk pk heterozygotes show severely reduced vesicle transport, with loss of both copies of pk pk showing a marked decrease i...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies

Ehaideb

Iyengar

Ueda³

et al. 2014

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

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“…whether it is via biochemical reactions or via microtubules (Shimada et al, 2006), is assumed to be at 164 the steady state, a constant g is used to reflect the consistent strength of intracellular signaling. 165…”

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confidence: 99%

Is anisotropic propagation of polarized molecular distribution the common mechanism of swirling patterns of planar cell polarization?

Zhu

2009

Journal of Theoretical Biology

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8Mutations in multiple planar cell polarity (PCP) genes can cause swirling patterns indicated by whorls 9 and tufts of hairs in the wings and the abdomen of Drosophila and in the skin of vertebrates. A c c e p t e d m a n u s c r i p t 2 molecular distribution may be the common mechanism of swirling patterns caused by different 24 mutations. It also suggests that at the cell level, as at the molecular level, a simple mechanism can 25 generate complex and diverse cellular patterns in different molecular contexts. The similarity between 26 the induced polarization and its propagation both in the epithelial cells and the dielectric molecules 27 also interestingly suggests some commonalities between pattern formation in the biological and 28 physical systems. 29

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“…However, alkaloids have numerous functions including analgesics, anti-inflammatory, antispasmodic and bactericidal effects 34 . Moreover, tannins display anticancer activity and inhibition of cell protein synthesis 35 . Also, steroidal extracts displayed antibacterial activities 36 , while flavonoids exhibit antimicrobial and antioxidant properties 37 .…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Composition and In vitro Antimicrobial, Antioxidant Activites of Methanolic Leaf Extracts From Excoecaria agallocha

A.G

et al. 2016

Biosci., Biotech. Res. Asia

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This study investigated the phytochemical, antimicrobial and antioxidant properties of methanolic leaf fractionated extracts of Excoecaria agallocha. Antibacterial activity test of fractionated extract of Excoecaria agallocha was conducted via Disk diffusion assay. Micro titer broth dilution technique was performed to determine the minimum inhibitory concentration (MIC) and Minimum Bactericidal Concentration (MBC). Qualitative and quantitative DPPH radical scavenging activity determines the antioxidant activity in E. agallocha. Chromatographic separation was completed using thin layer chromatography (TLC) and column chromatographic techniques. Phytochemical screening of fractionated extract revealed active constituents including alkaloids, saponins, flavonoids, terpenoid and tannins. In vitro antibacterial activity of columnfractionated extract demonstrated inhibitory effect against Flavobacterium indicum, Chryseobacterium meningosepticum, Chryseobacterium indologenes and Chryseobacterium gleum isolated from diseased fish. MIC and MBC of E. agallocha fractionated extract was 1.56 mg/ml and 3.12 mg/ml, respectively. TLC-based qualitative DPPH analysis revealed antioxidant activity in E. agallocha extract, specified by yellowish stain on maroon color TLC plate. These bands indicate the presence of various compounds that could act as potential antimicrobial agents. The present study indicates that E. agallocha leaves contain active phytochemicals which inhibit bacteria and could be useful in the treatment of microbial infections in fish.

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Polarized Transport of Frizzled along the Planar Microtubule Arrays in Drosophila Wing Epithelium

Cited by 272 publications

References 69 publications

prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies

prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies

Is anisotropic propagation of polarized molecular distribution the common mechanism of swirling patterns of planar cell polarization?

Phytochemical Composition and In vitro Antimicrobial, Antioxidant Activites of Methanolic Leaf Extracts From Excoecaria agallocha

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