Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
复制标题
果蝇皱纹/肌球蛋白VIIA 的突变破坏了小齿的形态发生。
DOI：
10.1016/j.ydbio.2020.11.007
复制
发表时间：
2021-03
影响因子：
2.7
通讯作者：
Kiehart DP
中科院分区：
文献类型：
--
作者：
Sallee JL;Crawford JM;Singh V;Kiehart DP
肌动蛋白丝的交联、成束和分子马达蛋白是微绒毛、静纤毛、毛发和刚毛等上皮突起组装所必需的。这些蛋白质的突变会导致这些肌动蛋白突起的形状、结构和功能缺陷。静纤毛形成所必需的一种蛋白质，肌球蛋白VIIA，是一种在整个胚胎发育过程中保守的肌动蛋白基马达蛋白。在黑腹果蝇中，MyoVIIA同源基因crinkled（ck）的严重突变是“半致死性”的，只有很小比例的果蝇存活到成年。这些幸存者表现出与头发和鬃毛中肌动蛋白成束相关的形态缺陷。为了更好地了解ck/MyoVIIA的功能，在肌动蛋白的结构，我们使用显性雌性不育的方法来分析损失的孕产妇和合子（M/Z）ck/MyoVIIA在形态发生的dennial，小肌动蛋白为基础的预测腹侧表皮的果蝇胚胎。M/Z ck突变体显示出严重的缺陷，在正确的位置启动的齿状突起的肌动蛋白丝，但未能伸长和束形成正常的投影。使用缺失突变体构建体，我们证明了C-末端MyTH 4和FERM结构域都是正确的小齿形成所必需的。此外，我们表明，CK/MyoVIIA基因相互作用与昏暗样（dyl），一个成员的ZPD家族的蛋白质，连接细胞外基质的质膜，突变时也破坏正常的齿状突的形成。单独的蛋白质的损失不会改变另一个的定位;然而，两种蛋白质一起的损失显著增强了当单独的蛋白质不存在时观察到的齿状突形状的缺陷。我们的数据表明，ck/MyoVIIA在肌动蛋白丝束的形成和/或组织中起着关键作用，肌动蛋白丝束驱动细胞投射的正确形状。
Actin filament crosslinking, bundling and molecular motor proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such proteins cause defects in the shape, structure, and function of these actin-based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin-based motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homologue crinkled (ck) are “semi-lethal” with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA’s function in bundled-actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin-based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology-actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C-terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky-like (dyl), a member of the ZPD family of proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
登录
查看更多内容
影响因子：
4
作者：
El-Amraoui, A;Petit, C
通讯作者：
Petit, C
DOI：
10.1073/pnas.0711149105
发表时间：
2008-07-01
影响因子：
11.1
作者：
Claessens, M. M. A. E.;Semmrich, C.;Bausch, A. R.
通讯作者：
Bausch, A. R.
影响因子：
64.8
作者：
GIBSON, F;WALSH, J;BROWN, SDM
通讯作者：
BROWN, SDM
影响因子：
3.5
作者：
Adato, A;Michel, V;Petit, C
通讯作者：
Petit, C
影响因子：
7.7
作者：
El-Amraoui, A;Schonn, JS;Petit, C
通讯作者：
Petit, C