The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes

Spradling, Allan C.; Stern, Dianne M.; Beaton, Amy; Rhem, E J; Laverty, Todd R.; Mozden, N; Misra, Sima; Rubin, Gerald M.

doi:10.1093/genetics/153.1.135

Cited by 694 publications

(34 citation statements)

References 215 publications

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“…PP2A B56 regulatory subunit type 2 (wellrounded): wrd KG01108 / wrd KG01108 (70). PP2A B''' (striatin) regulatory subunit (connector of kinase to AP-1): cka 05836 /cka S1883 (66,77). PP4 regulatory subunit PP4R3 (falafel): 795 (76).…”

Section: Fly Stocksmentioning

confidence: 99%

Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

Williams

Filter

Blake-Hodek

et al. 2014

eLife

100

194

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During M phase, Endosulfine (Endos) family proteins are phosphorylated by Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase PP2A-B55, which would otherwise prematurely reverse many CDK-driven phosphorylations. We show here that PP2A-B55 is the enzyme responsible for dephosphorylating pEndos during M phase exit. The kinetic parameters for PP2A-B55’s action on pEndos are orders of magnitude lower than those for CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55 regulation that we call inhibition by unfair competition. As the name suggests, during M phase PP2A-B55’s attention is diverted to pEndos, which binds much more avidly and is dephosphorylated more slowly than other substrates. When Gwl is inactivated during the M phase-to-interphase transition, the dynamic balance changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the phosphatase can refocus its attention on CDK-phosphorylated substrates. This mechanism explains simultaneously how PP2A-B55 and Gwl together regulate pEndos, and how pEndos controls PP2A-B55.DOI: http://dx.doi.org/10.7554/eLife.01695.001

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Section: Fly Stocksmentioning

confidence: 99%

Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

Williams

Filter

Blake-Hodek

et al. 2014

eLife

100

194

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“…To investigate washout function, we obtained a P-element insertion line, PfEPgy2gCG13176 EY15549 (ref [28]; BDGP, unpublished data), with a P-element insertion at the beginning of the washout coding region. These flies are homozygous viable with no apparent phenotype.…”

Section: Drosophila Wash Is Essentialmentioning

confidence: 99%

Human subtelomeric WASH genes encode a new subclass of the WASP family

Linardopoulou¹,

Parghi²,

Friedman³

et al. 2005

PLoS Genet

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Subtelomeres are duplication-rich, structurally variable regions of the human genome situated just proximal of telomeres. We report here that the most terminally located human subtelomeric genes encode a previously unrecognized third subclass of the Wiskott-Aldrich Syndrome Protein family, whose known members reorganize the actin cytoskeleton in response to extracellular stimuli. This new subclass, which we call WASH, is evolutionarily conserved in species as diverged as Entamoeba. We demonstrate that WASH is essential in Drosophila. WASH is widely expressed in human tissues, and human WASH protein colocalizes with actin in filopodia and lamellipodia. The VCA domain of human WASH promotes actin polymerization by the Arp2/3 complex in vitro. WASH duplicated to multiple chromosomal ends during primate evolution, with highest copy number reached in humans, whose WASH repertoires vary. Thus, human subtelomeres are not genetic junkyards, and WASH's location in these dynamic regions could have advantageous as well as pathologic consequences.

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“…Scer\FRT.hs3]=3'.RS5+3.3'}ED440;Ryder et al, 2004;Kyoto #150498) • Miro Sd32 (Guo et al, 2005) • Miro B682 (Guo et al, 2005;BL #52003) • Df(Miro) (Df(3R)Exel6197; Parks et al, 2004;BL #7676) • Klc 8ex94 (Gindhart et al, 1998;BL #31997) • syd z4 (Bowman et al, 2000;BL #32016) • Df(3L)syd A2 (Bowman et al, 2000;deleting C-terminus;BL #32017) • Pat1 grive and Pat1 robin (Loiseau et al, 2010;Isabel Palacios) • Sod1 n1 (Phillips et al, 1989;BL #24492) • Sod1 n64 (Phillips et al, 1995;BL #7451) • Rtnl1-YFP (PBac{681.P. FSVS-1}Rtnl1CPTI001291;Cahir O'Kane;O'Sullivan et al, 2012) • Drp1 T26 (Verstreken et al, 2005;BL #3662) • Marf B (Sandoval et al, 2014;Hugo Bellen) • P{lacW}Opa1 s3475 (Spradling et al, 1999;BL #12188) • Cat n1 (Mackay and Bewley, 1989; Matthias Landgraf) (Duttaroy et al, 2003;BL#34060) • Pex3 2 (Faust et al, 2014;BL#64251) Gal4 driver lines used were the • elav-Gal4 (Luo et al, 1994) • tubP-Gal4 (Lee and Luo, 1999;Liqun Luo)…”

Section: Fly Stocksmentioning

confidence: 99%

New cell biological explanations for kinesin-linked axon degeneration

Liew

Voelzmann

Pinho-Correia

et al. 2021

Preprint

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Axons are the slender, up to meter-long projections of neurons that form the biological cables wiring our bodies. Most of these delicate structures must survive for an organism's lifetime, meaning up to a century in humans. Axon maintenance requires life-sustaining motor protein-driven transport distributing materials and organelles from the distant cell body. It seems logic that impairing this transport causes systemic deprivation linking to axon degeneration. But the key steps underlying these pathological processes are little understood. To investigate mechanisms triggered by motor protein aberrations, we studied more than 40 loss- and gain-of-function conditions of motor proteins, cargo linkers or further genes involved in related processes of cellular physiology. We used one standardised Drosophila primary neuron system and focussed on the organisation of axonal microtubule bundles as an easy to assess readout reflecting axon integrity. We found that bundle disintegration into curled microtubules is caused by the losses of Dynein heavy chain and the Kif1 and Kif5 homologues Unc-104 and Kinesin heavy chain (Khc). Using point mutations of Khc and functional loss of its linker proteins, we studied which of Khc's sub-functions might link to microtubule curling. One cause was emergence of harmful reactive oxygen species through loss of Milton/Miro-mediated mitochondrial transport. In contrast, loss of the Kinesin light chain linker caused microtubule curling through an entirely different mechanism appearing to involve increased mechanical challenge to microtubule bundles through de-inhibition of Khc. The wider implications of our findings for the understanding of axon maintenance and pathology are discussed.

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The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes

Cited by 694 publications

References 215 publications

Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers

Human subtelomeric WASH genes encode a new subclass of the WASP family

New cell biological explanations for kinesin-linked axon degeneration

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