aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda inDrosophilaneuroblasts

Abstract

SUMMARY 10Cell fate generation can rely on the unequal distribution of molecules during 11 progenitor cell division in the nervous system of vertebrates and 12invertebrates. Here we address asymmetric fate determinant localization in 13 the developing Drosophila nervous system, focussing on the control of 14 asymmetric Miranda distribution in larval neuroblasts. We used live imaging of 15 neuroblast polarity reporters at endogenous levels of expression to address 16Miranda localization during the cell cycle. We reveal that the regulation and 17 dynamics of cortical association of Miranda in interphase and mitosis are 18 different. In interphase Miranda binds directly to the plasma membrane. At 19 the onset of mitosis, Miranda is phosphorylated by aPKC and displaced from 20 the PM. After nuclear envelope breakdown asymmetric localization of Miranda 21 requires actomyosin activity. Therefore, Miranda phosphorylation by aPKC and 22 differential binding to the actomyosin network are required at distinct phases 23 of the cell cycle to polarize fate determinant localization. 24