Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
Mol Biol Cell. 2012 Nov;23(22):4465-71. doi: 10.1091/mbc.E12-09-0655. Epub 2012 Sep 26.
Polarity landmarks guide epithelial development. In the early Drosophila ectoderm, the scaffold protein Bazooka (Drosophila PAR-3) forms apicolateral landmarks to direct adherens junction assembly. However, it is unclear how Bazooka becomes polarized. We report two mechanisms acting in concert to displace Bazooka from the basolateral membrane. As cells form during cellularization, basally localized Bazooka undergoes basal-to-apical transport. Bazooka requires its three postsynaptic density 95, discs large, zonula occludens-1 (PDZ) domains to engage the transport mechanism, but with the PDZ domains deleted, basolateral displacement still occurs by gastrulation. Basolateral PAR-1 activity appears to act redundantly with the transport mechanism. Knockdown of PAR-1 sporadically destabilizes cellularization furrows, but basolateral displacement of Bazooka still occurs by gastrulation. In contrast, basolateral Bazooka displacement is blocked with disruption of both the transport mechanism and phosphorylation by PAR-1. Thus Bazooka is polarized through a combination of transport and PAR-1-induced dispersion from basolateral membranes. Our work complements recent findings in Caenorhabditis elegans and thus suggests the coupling of transport and dispersion is a common protein polarization strategy.
极性地标指导上皮细胞的发育。在早期果蝇外胚层中,支架蛋白 Bazooka(果蝇 PAR-3)形成顶端侧地标,以指导黏着连接组装。然而,Bazooka 如何极化尚不清楚。我们报告了两种协同作用的机制,将 Bazooka 从基底外侧膜上置换下来。在细胞化过程中,基底定位的 Bazooka 经历基底到顶端的运输。Bazooka 需要其三个突触后密度 95、Discs 大、Zonula occludens-1(PDZ)结构域来参与运输机制,但 PDZ 结构域缺失后,通过原肠胚形成仍会发生基底外侧置换。基底外侧 PAR-1 活性似乎与运输机制冗余。PAR-1 的敲低偶尔会破坏细胞化皱襞,但通过原肠胚形成仍会发生基底外侧 Bazooka 的置换。相比之下,破坏运输机制和 PAR-1 磷酸化都会阻止 Bazooka 的基底外侧置换。因此,Bazooka 通过运输和 PAR-1 诱导的从基底外侧膜上的分散的组合而极化。我们的工作补充了最近在秀丽隐杆线虫中的发现,因此表明运输和分散的偶联是一种常见的蛋白质极化策略。