CDKL5 regulates flagellar length and localizes to the base of the flagella in Chlamydomonas.
CDKL5 regulates flagellar length and localizes to the base of the flagella in Chlamydomonas.
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DOI：
10.1091/mbc.e12-10-0718
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发表时间：
2013-03
影响因子：
3.3
通讯作者：
Lefebvre PA
中科院分区：
文献类型：
--
作者：
Tam LW;Ranum PT;Lefebvre PA
LF 5编码一种与人CDKL 5同源的蛋白激酶，LF 5中的两个突变导致衣原体鞭毛异常长。在WT细胞中，LF 5 p定位于鞭毛的非常近端区域受其他三种LF基因产物的调节，这三种LF基因产物构成了细胞质长度调节复合物。衣原体鞭毛的长度受到严格控制。四个基因LF 1、LF 2、LF 3和LF 4的突变导致细胞组装鞭毛，其长度可达野生型的三倍。LF 2和LF 4编码蛋白激酶。在这里，我们描述了一个新的基因，LF 5，其中无效突变导致细胞组装鞭毛的多余长度。LF 5基因编码的蛋白激酶在序列上与蛋白激酶CDKL 5非常相似。在人类中，这种激酶的突变会导致严重的青少年癫痫。LF 5蛋白定位于一个独特的位置：鞭毛的近端1 μm。当构成细胞质长度调节复合物（LRC）中的蛋白质的基因-LF 1、LF 2和LF 3-突变时，LF 5蛋白的近端定位丢失。在这些突变体中，LF 5 p变得位于鞭毛的远端或沿着鞭毛长度，表明长度调节至少部分涉及LRC对LF 5 p定位的控制。
Two mutations in LF5, which encodes a protein kinase orthologous to human CDKL5, cause abnormally long flagella in Chlamydomonas. The localization of LF5p to the very proximal region of flagella in WT cells is regulated by three other LF gene products, which make up the cytoplasmic length regulatory complex. The length of Chlamydomonas flagella is tightly regulated. Mutations in four genes—LF1, LF2, LF3, and LF4—cause cells to assemble flagella up to three times wild-type length. LF2 and LF4 encode protein kinases. Here we describe a new gene, LF5, in which null mutations cause cells to assemble flagella of excess length. The LF5 gene encodes a protein kinase very similar in sequence to the protein kinase CDKL5. In humans, mutations in this kinase cause a severe form of juvenile epilepsy. The LF5 protein localizes to a unique location: the proximal 1 μm of the flagella. The proximal localization of the LF5 protein is lost when genes that make up the proteins in the cytoplasmic length regulatory complex (LRC)—LF1, LF2, and LF3—are mutated. In these mutants LF5p becomes localized either at the distal tip of the flagella or along the flagellar length, indicating that length regulation involves, at least in part, control of LF5p localization by the LRC.