CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation.
CSPP is a ciliary protein interacting with Nephrocystin 8 and required for cilia formation.
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DOI：
10.1091/mbc.e09-06-0503
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发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Stokke T
中科院分区：
文献类型：
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作者：
Patzke S;Redick S;Warsame A;Murga-Zamalloa CA;Khanna H;Doxsey S;Stokke T
CSPP和CSPP-L是已知有丝分裂功能的中心体蛋白。在这里，我们确定CSPP蛋白作为纤毛蛋白，并将它们放入NPHP蛋白网络中，这对正常纤毛依赖性肾脏和视网膜组织结构至关重要。重要的是，发现CSPP-L是纤毛发生所需的，并且显示为纤毛长度调节剂。我们以前描述了细胞周期和微管相关的功能的两个剪接异构体的中心体纺锤体极相关蛋白（CSPP和CSPP-L）。在这里，我们表明，内源性CSPP亚型不仅定位于中心体和中间体的周期细胞，但也延伸到纤毛轴丝在有丝分裂后的静息细胞。它们是体外hTERT-RPE 1细胞中纤毛发生所需的，并在体内纤毛肾、视网膜和呼吸细胞中表达。我们报告，CSPP亚型需要其共同的C-末端结构域相互作用与肾囊蛋白8（NPHP 8/RPGRIP 1 L），并形成三元复合物与NPHP 8和NPHP 4。我们发现CSPP-L是NPHP 8有效定位所需的，而不是NPHP 4到基体。然而，hTERT-RPE 1细胞中的纤毛发生缺陷不是通过NPHP 8的缺失介导的。类似于CSPP-L的异位表达的效果，纤毛长度在NPHP 8耗尽的细胞中增加。因此，我们的研究结果表明，CSPP蛋白可能参与进一步的细胞骨架组织的基体和初级纤毛。总之，我们已经确定了一种新的，非有丝分裂功能的CSPP蛋白，将它们放置到一个纤毛蛋白网络的正常肾脏和视网膜组织结构和生理学的关键。
CSPP and CSPP-L are centrosomal proteins of known mitotic function. Here, we identify CSPP proteins as ciliary proteins and place them into a NPHP protein network crucial for normal cilia-dependent renal and retinal tissue architecture. Importantly, CSPP-L is found to be required for ciliogenesis and shown to be a cilia length modulator. We described previously the cell cycle- and microtubule-related functions of two splice isoforms of the centrosome spindle pole-associated protein (CSPP and CSPP-L). Here, we show that endogenous CSPP isoforms not only localize to centrosomes and the midbody in cycling cells but also extend to the cilia axoneme in postmitotic resting cells. They are required for ciliogenesis in hTERT-RPE1 cells in vitro and are expressed in ciliated renal, retinal, and respiratory cells in vivo. We report that CSPP isoforms require their common C-terminal domain to interact with Nephrocystin 8 (NPHP8/RPGRIP1L) and to form a ternary complex with NPHP8 and NPHP4. We find CSPP-L to be required for the efficient localization of NPHP8 but not NPHP4 to the basal body. The ciliogenesis defect in hTERT-RPE1 cells is, however, not mediated through loss of NPHP8. Similar to the effects of ectopical expression of CSPP-L, cilia length increased in NPHP8-depleted cells. Our results thus suggest that CSPP proteins may be involved in further cytoskeletal organization of the basal body and its primary cilium. To conclude, we have identified a novel, nonmitotic function of CSPP proteins placing them into a ciliary protein network crucial for normal renal and retinal tissue architecture and physiology.
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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：
3.5
作者：
Delous M;Hellman NE;Gaudé HM;Silbermann F;Le Bivic A;Salomon R;Antignac C;Saunier S
通讯作者：
Saunier S
影响因子：
13.6
作者：
Fliegauf, Manfred;Horvath, Judit;Omran, Heymut
通讯作者：
Omran, Heymut
影响因子：
3.2
作者：
GORDON, RE;LANE, BP;MILLER, F
通讯作者：
MILLER, F
影响因子：
64.8
作者：
通讯作者：
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