Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Cell Rep. 2024 Mar 26;43(3):113823. doi: 10.1016/j.celrep.2024.113823. Epub 2024 Feb 21.
During asymmetric division of Drosophila larval neuroblasts, the fate determinant Prospero (Pros) and its adaptor Miranda (Mira) are segregated to the basal cortex through atypical protein kinase C (aPKC) phosphorylation of Mira and displacement from the apical cortex, but Mira localization after aPKC phosphorylation is not well understood. We identify Kin17, a DNA replication and repair protein, as a regulator of Mira localization during asymmetric cell division. Loss of Kin17 leads to aberrant localization of Mira and Pros to the centrosome, cytoplasm, and nucleus. We provide evidence to show that the mislocalization of Mira and Pros is likely due to reduced expression of Falafel (Flfl), a component of protein phosphatase 4 (PP4), and defects in dephosphorylation of serine-96 of Mira. Our work reveals that Mira is likely dephosphorylated by PP4 at the centrosome to ensure proper basal localization of Mira after aPKC phosphorylation and that Kin17 regulates PP4 activity by regulating Flfl expression.
在果蝇幼虫神经母细胞的不对称分裂过程中，命运决定因子 Prospero（Pros）及其衔接蛋白 Miranda（Mira）通过非典型蛋白激酶 C（aPKC）对 Mira 的磷酸化以及从顶端皮层的位移被分配到基底皮层，但 aPKC 磷酸化后 Mira 的定位尚不清楚。我们确定 Kin17，一种 DNA 复制和修复蛋白，是不对称细胞分裂过程中 Mira 定位的调节剂。Kin17 的缺失导致 Mira 和 Pros 异常定位于中心体、细胞质和细胞核。我们提供的证据表明，Mira 和 Pros 的定位错误可能是由于蛋白磷酸酶 4（PP4）的组成部分 Falafel（Flfl）的表达减少以及 Mira 丝氨酸 96 的去磷酸化缺陷所致。我们的工作表明，Mira 可能在中心体被 PP4 去磷酸化，以确保 aPKC 磷酸化后 Mira 的基底正确定位，并且 Kin17 通过调节 Flfl 的表达来调节 PP4 的活性。
