Cell Biology Laboratories, School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, UK, BS8 1TD.
School of Physiology and Pharmacology, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, UK, BS8 1TD.
J Cell Sci. 2018 May 4;131(9):jcs212258. doi: 10.1242/jcs.212258.
Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies, which are characterised by debilitating developmental defects that affect many tissues. Here, we report a new role for regulator of calcineurin 2 (RCAN2) in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing. In contrast to previous work where we showed that depletion of giantin by RNAi results in defects in ciliogenesis and in cilia length control, giantin knockout cells generate normal cilia after serum withdrawal. Furthermore, giantin knockout zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2 expression in giantin knockout cells results in the same defects in the control of cilia length that are seen upon RNAi of giantin itself. Together, these data define RCAN2 as a regulator of cilia function that can compensate for the loss of giantin function.
人体内几乎每个细胞都延伸出一根初级纤毛。纤毛功能缺陷会导致一组被称为纤毛病的疾病，其特征是影响许多组织的衰弱性发育缺陷。在这里，我们报告了钙调神经磷酸酶 2 调节因子（RCAN2）在初级纤毛功能中的新作用。它定位于中心体和基底体，需要维持正常的纤毛长度。通过对高尔基基质蛋白 giantin 基因编辑敲除细胞的比较 RNAseq 分析，RCAN2 被鉴定为表达上调最明显的基因。与我们之前的工作相反，我们发现 giantin 的 RNAi 敲低导致纤毛发生和纤毛长度控制缺陷，而 giantin 敲除细胞在血清去除后会产生正常的纤毛。此外，gaintin 敲除斑马鱼表现出 RCAN2 的表达增加。重要的是，在 giantin 敲除细胞中抑制 RCAN2 的表达会导致与 giantin RNAi 本身一样的纤毛长度控制缺陷。这些数据共同定义了 RCAN2 作为纤毛功能的调节剂，它可以补偿 giantin 功能的丧失。
