Casein kinase II and calcineurin modulate TRPP function and ciliary lcalization
Casein kinase II and calcineurin modulate TRPP function and ciliary lcalization
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DOI：
10.1091/mbc.e05-10-0935
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Barr, MM
中科院分区：
文献类型：
--
作者：
Hu, JH;Bae, YK;Barr, MM
纤毛作为多种生物的感觉装置，它们的缺陷导致许多人类疾病。在肾细胞的初级纤毛中，瞬时受体电位多囊蛋白（TRPP）通道多囊蛋白-1（PC-1）和多囊蛋白-2（PC-2）充当机械敏感性通道，其缺陷导致常染色体显性多囊肾病。在秀丽隐杆线虫雄性特异性神经元的感觉纤毛中，TRPPs LOV-1和PKD-2是交配行为所必需的。调节TRPP纤毛定位和功能的机制在很大程度上是未知的。我们确定了丝氨酸-苏氨酸酪蛋白激酶II（CK 2）的调节亚基作为LOV-1和人PC-1的结合伴侣。CK 2和钙调磷酸酶TAX-6调节雄性交配行为和PKD-2纤毛定位。磷酸缺陷突变体PKD-2（S534 A）定位于纤毛，而磷酸模拟PKD-2（S534 D）突变体在纤毛中基本不存在。钙调神经磷酸酶是PKD-2纤毛定位所必需的，但对于纤毛基因表达、纤毛发生或纤毛结构成分的定位不是必需的。钙调神经磷酸酶的这种意想不到的功能可能对调节纤毛蛋白定位很重要。一个动态的磷酸化-去磷酸化循环可能代表了一种调节TRPP活性、细胞感觉和纤毛蛋白定位的机制。
Cilia serve as sensory devices in a diversity of organisms and their defects contribute to many human diseases. In primary cilia of kidney cells, the transient receptor potential polycystin (TRPP) channels polycystin-1 (PC-1) and polycystin-2 (PC-2) act as a mechanosensitive channel, with defects resulting in autosomal dominant polycystic kidney disease. In sensory cilia of Caenorhabditis elegans male-specific neurons, the TRPPs LOV-1 and PKD-2 are required for mating behavior. The mechanisms regulating TRPP ciliary localization and function are largely unknown. We identified the regulatory subunit of the serine-threonine casein kinase II (CK2) as a binding partner of LOV-1 and human PC-1. CK2 and the calcineurin phosphatase TAX-6 modulate male mating behavior and PKD-2 ciliary localization. The phospho-defective mutant PKD-2(S534A) localizes to cilia, whereas a phospho-mimetic PKD-2(S534D) mutant is largely absent from cilia. Calcineurin is required for PKD-2 ciliary localization, but is not essential for ciliary gene expression, ciliogenesis, or localization of cilium structural components. This unanticipated function of calcineurin may be important for regulating ciliary protein localization. A dynamic phosphorylation-dephosphorylation cycle may represent a mechanism for modulating TRPP activity, cellular sensation, and ciliary protein localization.