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First published online 28 November 2007
doi: 10.1242/dev.011437


Development 135, 53-63 (2008)
Published by The Company of Biologists 2008


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Sisyphus, the Drosophila myosin XV homolog, traffics within filopodia transporting key sensory and adhesion cargos

Raymond Liu1, Sarah Woolner1,2,*, James E. Johndrow1,*, David Metzger1,*, Adriana Flores1,* and Susan M. Parkhurst1,{dagger}

1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2 MRC-LMCB, University College London, London WC1E 6BT, UK.

{dagger} Author for correspondence (e-mail: susanp{at}fhcrc.org)

Accepted 28 September 2007

Unconventional myosin proteins of the MyTH-FERM superclass are involved in intrafilopodial trafficking, are thought to be mediators of membrane-cytoskeleton interactions, and are linked to several forms of deafness in mammals. Here we show that the Drosophila myosin XV homolog, Sisyphus, is expressed at high levels in leading edge cells and their cellular protrusions during the morphogenetic process of dorsal closure. Sisyphus is required for the correct alignment of cells on opposing sides of the fusing epithelial sheets, as well as for adhesion of the cells during the final zippering/fusion phase. We have identified several putative Sisyphus cargos, including DE-cadherin (also known as Shotgun) and the microtubule-linked proteins Katanin-60, EB1, Milton and aPKC. These cargos bind to the Sisyphus FERM domain, and their binding is in some cases mutually exclusive. Our data suggest a mechanism for Sisyphus in which it maintains a balance between actin and microtubule cytoskeleton components, thereby contributing to cytoskeletal cross-talk necessary for regulating filopodial dynamics during dorsal closure.

Key words: Unconventional myosin, Myosin XV, Dorsal closure, Filopodia, Microtubules, Actin, Cytoskeleton, DE-cadherin (Shotgun), EB1, {alpha}-tubulin, Drosophila


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