Vaccari Thomas, Rabouille Catherine, Ephrussi Anne
Developmental Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Curr Biol. 2005 Feb 8;15(3):255-61. doi: 10.1016/j.cub.2005.01.033.
The Ser/Thr kinases of the PAR-1/MARK/Kin1 family are conserved regulators of polarity in epithelial and non-epithelial cells . Drosophila PAR-1 localizes laterally in the follicular epithelium of the ovary , where it has been shown to function at two distinct levels: It stabilizes the cytoskeleton and it regulates apical-basal polarity by directly inhibiting lateral assembly of the apical aPKC/Bazooka/PAR-6 complex . However, it has been unclear how lateral localization of Drosophila PAR-1 is achieved and whether this localization contributes to epithelial polarity in vivo. Here we show that, through its spacer domain, Drosophila PAR-1 accumulates on the lateral plasma membrane (PM) in cells of the follicular epithelium (FE). Rescue experiments indicate that in FE cells PAR-1 kinase activity is essential for all the described functions of PAR-1. In contrast, the spacer domain of PAR-1 is required for apical-basal polarity and growth control but is dispensable for microtubule (MT) stabilization. Our data indicate that the spacer domain of PAR-1 is required for lateral PM localization of PAR-1 kinase and for development of a polarized FE.
PAR-1/MARK/Kin1家族的丝氨酸/苏氨酸激酶是上皮细胞和非上皮细胞极性的保守调节因子。果蝇PAR-1定位于卵巢滤泡上皮的侧面,在那里它已被证明在两个不同水平发挥作用:它稳定细胞骨架,并通过直接抑制顶端非典型蛋白激酶C/巴祖卡蛋白/PAR-6复合物的侧向组装来调节顶端-基部极性。然而,尚不清楚果蝇PAR-1的侧向定位是如何实现的,以及这种定位在体内是否有助于上皮极性。在这里,我们表明,果蝇PAR-1通过其间隔结构域在滤泡上皮(FE)细胞的侧向质膜(PM)上积累。拯救实验表明,在FE细胞中,PAR-1激酶活性对于PAR-1的所有所述功能至关重要。相比之下,PAR-1的间隔结构域对于顶端-基部极性和生长控制是必需的,但对于微管(MT)稳定是可有可无的。我们的数据表明,PAR-1的间隔结构域对于PAR-1激酶的侧向PM定位和极化FE的发育是必需的。