Yeh Anna R, Hoeprich Gregory J, McDougal Anthony, Goode Bruce L, Martin Adam C
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biology, Brandeis University, Waltham, MA, USA.
bioRxiv. 2025 Jun 21:2023.04.17.537198. doi: 10.1101/2023.04.17.537198.
Actin networks undergo rearrangements that influence cell and tissue shape. Actin network assembly and organization is regulated in space and time by a host of actin binding proteins. The Synaptotagmin-like protein, Bitesize (Btsz), is known to organize actin at epithelial cell apical junctions in a manner that depends on its interaction with the actin-binding protein, Moesin. Using RNAi, we showed that Btsz functions at earlier, syncytial stages of embryo development. Btsz is required to stabilize pseudo-cleavage furrows that prevent metaphase spindle collisions and nuclear fallout prior to cellularization. While previous studies have focused on Btsz function through Moesin, we find that phosphorylated Moesin localized to the nuclear envelope and was not enriched at pseudo-cleavage furrows, suggesting a Moesin- independent function for Btsz in syncytial embryos. Consistent with this, mutants that affected all Moesin binding domain isoforms did not recapitulate pan-isoform Btsz depletion and we find that the C-terminal half of Btsz cooperatively binds to and bundles F-actin. We propose that Synaptotagmin-like proteins directly regulate actin organization during syncytial development.
肌动蛋白网络会发生重排，影响细胞和组织的形状。肌动蛋白网络的组装和组织在空间和时间上受到多种肌动蛋白结合蛋白的调节。已知类似突触结合蛋白的小蛋白（Btsz）以一种依赖于其与肌动蛋白结合蛋白膜突蛋白相互作用的方式，在上皮细胞顶端连接处组织肌动蛋白。通过RNA干扰，我们发现Btsz在胚胎发育的早期合胞体阶段发挥作用。Btsz是稳定假分裂沟所必需的，这些假分裂沟可防止在细胞化之前中期纺锤体碰撞和细胞核脱落。虽然先前的研究集中在Btsz通过膜突蛋白发挥的功能上，但我们发现磷酸化的膜突蛋白定位于核膜，在假分裂沟处并不富集，这表明Btsz在合胞体胚胎中具有不依赖于膜突蛋白的功能。与此一致的是，影响所有膜突蛋白结合结构域异构体的突变体并不能重现全异构体Btsz缺失的情况，并且我们发现Btsz的C端一半能协同结合并捆绑F-肌动蛋白丝。我们提出，类似突触结合蛋白的蛋白质在合胞体发育过程中直接调节肌动蛋白的组织。
