Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease.
Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease.
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DOI：
10.1038/ng.2715
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发表时间：
2013-09
期刊：
影响因子：
30.8
通讯作者：
Somlo, Stefan
中科院分区：
文献类型：
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作者：
Ma, Ming;Tian, Xin;Igarashi, Peter;Pazour, Gregory J.;Somlo, Stefan
肾囊肿发生在完整纤毛中的多囊蛋白失活后，或通过鞭毛内转运相关蛋白失活而完全去除纤毛后。我们通过将多囊蛋白的条件灭活与发育中和成年肾脏和肝脏中纤毛的同时消融相结合，研究了这两个不同过程中囊肿形成的机制。我们发现，多囊蛋白失活后，完整纤毛的丢失会抑制囊肿生长，并且囊肿疾病的严重程度与多囊蛋白最初丢失和随后纤毛退化之间的时间长度直接相关。这种纤毛依赖性囊肿生长不能通过 MAPK/ERK、mTOR 或 cAMP 通路的激活来解释，并且可能与纤毛完全丧失后囊肿生长的机制不同。这些数据证实了一条新途径的存在，该途径由多囊蛋白依赖性抑制和纤毛依赖性激活定义，可促进囊肿快速生长。
Kidney cysts occur following inactivation of polycystins in otherwise intact cilia or following complete removal of cilia by inactivation of intraflagellar transport-related proteins. We investigated the mechanisms of cyst formation in these two distinct processes by combining conditional inactivation of polycystins with concomitant ablation of cilia in developing and adult kidney and liver. We found that loss of intact cilia suppresses cyst growth following inactivation of polycystins and that the severity of cystic disease was directly related to the length of time between the initial loss of the polycystin proteins and the subsequent involution of cilia. This cilia-dependent cyst growth was not explained by activation of the MAPK/ERK, mTOR or cAMP pathways and is likely to be distinct from the mechanism of cyst growth following complete loss of cilia. The data establish the existence of a novel pathway defined by polycystin-dependent inhibition and cilia-dependent activation that promotes rapid cyst growth.
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影响因子：
10.5
作者：
Harris PC;Torres VE
通讯作者：
Torres VE
影响因子：
2.9
作者：
Gallagher AR;Germino GG;Somlo S
通讯作者：
Somlo S
影响因子：
3.5
作者：
Patel, Vishal;Li, Ling;Igarashi, Peter
通讯作者：
Igarashi, Peter
Chlamydomonas Reinhardtii鞭毛中PKD2的功能和动力学。
DOI：
10.1083/jcb.200704069
发表时间：
2007-11-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Huang K;Diener DR;Mitchell A;Pazour GJ;Witman GB;Rosenbaum JL
通讯作者：
Rosenbaum JL
影响因子：
30.8
作者：
通讯作者：
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