In the absence of Crumbs, myosin V is degraded, resulting in defective rhodopsin 1 transport to the rhabdomere and subsequent photoreceptor degeneration

Alloway

Anna Shevchenko

Bachmann

Belote

Berger

Borst

Bulgakova

Chinchore

den Hollander

Elisabeth Knust

Grawe

Griciuc

Izaddoost

Johnson

Kennan

Kiselev

Klebes

Krauss

Kumar

Nichols

Pellikka

Peng

Pocha

Richard

Rodionov

Rogers

Rosenbaum

Satoh

Shevchenko

Shirin Meher Pocha

Tabuchi

Tepass

Wang

Wodarz

Woolner

English

PubMed

The evolutionarily conserved Crumbs (Crb) complex is crucial for photoreceptor morphogenesis and homeostasis. Loss of Crb results in light-dependent retinal degeneration, which is prevented by feeding mutant flies carotenoid-deficient medium. This suggests a defect in rhodopsin 1 (Rh1) processing, transport, and/or signaling, causing degeneration; however, the molecular mechanism of this remained elusive. In this paper, we show that myosin V (MyoV) coimmunoprecipitated with the Crb complex and that loss of crb led to severe reduction in MyoV levels, which could be rescued by proteasomal inhibition. Loss of MyoV in crb mutant photoreceptors was accompanied by defective transport of the MyoV cargo Rh1 to the light-sensing organelle, the rhabdomere. This resulted in an age-dependent accumulation of Rh1 in the photoreceptor cell (PRC) body, a well-documented trigger of degeneration. We conclude that Crb protects against degeneration by interacting with and stabilizing MyoV, thereby ensuring correct Rh1 trafficking. Our data provide, for the first time, a molecular mechanism for the light-dependent degeneration of PRCs observed in crb mutant retinas

Pocha, Shirin

Shevchenko, Anna

Knust, Elisabeth

Max Planck Society eDoc Server

Crumbs regulates rhodopsin transport by interacting with and stabilizing myosin V

Pocha, S.

Shevchenko, A.

Knust, E.

MPG.PuRe

The evolutionarily conserved Crumbs (Crb) complex is crucial for photoreceptor morphogenesis and homeostasis. Loss of Crb results in light-dependent retinal degeneration, which is prevented by feeding mutant flies carotenoid-deficient medium. This suggests a defect in rhodopsin 1 (Rh1) processing, transport, and/or signaling, causing degeneration; however, the molecular mechanism of this remained elusive. In this paper, we show that myosin V (MyoV) coimmunoprecipitated with the Crb complex and that loss of crb led to severe reduction in MyoV levels, which could be rescued by proteasomal inhibition. Loss of MyoV in crb mutant photoreceptors was accompanied by defective transport of the MyoV cargo Rh1 to the light-sensing organelle, the rhabdomere. This resulted in an age-dependent accumulation of Rh1 in the photoreceptor cell (PRC) body, a well-documented trigger of degeneration. We conclude that Crb protects against degeneration by interacting with and stabilizing MyoV, thereby ensuring correct Rh1 trafficking. Our data provide, for the first time, a molecular mechanism for the light-dependent degeneration of PRCs observed in crb mutant retinas.</jats:p

Crossref

The Journal of Cell Biology

A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila.

Crumbs, the Drosophila homologue of human CRB1/ RP12, is essential for photoreceptor morphogenesis. Nature. 416:143– 149. http://dx.doi.org/10.1038/nature721

Inactivation of VCP/ter94 suppresses retinal pathology caused by misfolded rhodopsin in Drosophila. PLoS Genet. 6:e1001075. http://dx.doi .org/10.1371/journal.pgen.1001075

Myosin V, Rab11, and dRip11 direct apical secretion and cellular morphogenesis in developing Drosophila photoreceptors.

Protein identification by LC MS/MS LC-MS/MS analysis was performed on an UltiMate 3000 Nano LC System (Dionex) interfaced online to a linear ion trap LTQ mass spectrometer (Thermo Fisher Scientific), as described in Shevchenko

Quantification of MyoV fluorescence Image processing was performed using Fiji. Total MyoV fluorescence levels were obtained from WT and crb mutant tissue, normalized first to the number JCB •

Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors.

Rhodopsin plays an essential structural role in Drosophila photoreceptor development.

The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration.

Towards the comparative proteome by accurate mapping of the yeast proteomic environment. Genome Biol.

Unraveling the genetic complexity of Drosophila stardust during photoreceptor morphogenesis and prevention of light-induced degeneration.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3257572

Crumbs regulates rhodopsin transport by interacting with and stabilizing myosin V

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