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

Sisyphus, the Drosophila myosin XV homolog, traffics within filopodia transporting key sensory and adhesion cargos
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DOI:
10.1242/dev.011437
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发表时间:
2008-01-01
期刊:
影响因子:
4.6
通讯作者:
Parkhurst, Susan M.
Parkhurst, Susan M.
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, Raymond;Woolner, Sarah;Parkhurst, Susan M.

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MyTH-FERM超类的非常规肌球蛋白参与丝状伪足内运输,被认为是膜-细胞骨架相互作用的介质,并与哺乳动物的几种形式的耳聋有关。在这里,我们表明,果蝇肌球蛋白XV同源物,西西弗斯,在高水平表达的前缘细胞和它们的细胞突起在形态发生过程中的背关闭。Sisyphus是融合上皮片相对侧上的细胞正确对齐所必需的,以及在最终拉链/融合阶段期间细胞的粘附所必需的。我们已经确定了几个假定的西西弗斯货物,包括DE-钙粘蛋白(也称为猎枪)和微管连接蛋白Katanin-60,EB 1,米尔顿和aPKC。这些货物结合到西西弗斯FERM结构域,并且它们的结合在某些情况下是相互排斥的。我们的数据表明,西西弗斯的机制,它保持了肌动蛋白和微管细胞骨架成分之间的平衡,从而有助于细胞骨架的串扰调节丝状伪足的动力学在背关闭。
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.