Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, 100871, Beijing, China.
Center for Quantitative Biology, Peking University, 100871, Beijing, China.
Nat Commun. 2018 Oct 30;9(1):4511. doi: 10.1038/s41467-018-06990-9.
The primary cilium is elongated from the mother centriole and has diverse signaling roles during development and disease. The CP110-CEP97 complex functions as a negative regulator of ciliogenesis, although the mechanisms regulating its mother centriole localization are poorly understood. Here we show that M-Phase Phosphoprotein 9 (MPP9) is recruited by Kinesin Family Member 24 (KIF24) to the distal end of mother centriole where it forms a ring-like structure and recruits CP110-CEP97 by directly binding CEP97. Loss of MPP9 causes abnormal primary cilia formation in growing cells and mouse kidneys. After phosphorylation by Tau Tubulin Kinase 2 (TTBK2) at the beginning of ciliogenesis, MPP9 is targeted for degradation via the ubiquitin-proteasome system, which facilitates the removal of CP110 and CEP97 from the distal end of the mother centriole. Thus, MPP9 acts as a regulator of ciliogenesis by regulating the localization of CP110-CEP97 at the mother centriole.
初级纤毛从母中心粒伸长，在发育和疾病过程中有多种信号作用。CP110-CEP97 复合物作为纤毛发生的负调节剂，尽管其母中心粒定位的调节机制尚不清楚。在这里，我们显示 M 期磷酸蛋白 9 (MPP9) 被驱动蛋白家族成员 24 (KIF24) 募集到母中心粒的远端，在那里它形成一个环状结构，并通过直接结合 CEP97 招募 CP110-CEP97。MPP9 的缺失导致生长细胞和小鼠肾脏中初级纤毛的异常形成。在纤毛发生开始时被微管相关蛋白 Tau 激酶 2 (TTBK2) 磷酸化后，MPP9 通过泛素-蛋白酶体系统被靶向降解，这有利于 CP110 和 CEP97 从母中心粒的远端去除。因此，MPP9 通过调节 CP110-CEP97 在母中心粒上的定位来调节纤毛发生。
