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  Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length.

Zheng, X., Ramani, A., Soni, K., Gottardo, M., Zheng, S., Gooi, L. M., et al. (2016). Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length. Nature Communications, 7: 11874.

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Zheng, Xiangdong, Autor
Ramani, Anand, Autor
Soni, Komal, Autor
Gottardo, Marco, Autor
Zheng, Shuangping, Autor
Gooi, Li Ming, Autor
Li, Wenjing, Autor
Feng, Shan, Autor
Mariappan, Aruljothi, Autor
Wason, Arpit, Autor
Widlund, Per1, Autor           
Pozniakovsky, Andrei I.2, Autor           
Poser, Ina2, Autor           
Deng, Haiteng, Autor
Ou, Guangshuo, Autor
Riparbelli, Maria, Autor
Giuliano, Callaini, Autor
Hyman, Anthony2, Autor           
Sattler, Michael, Autor
Gopalakrishnan, Jay1, Autor           
Li, Haitao, Autor mehr..
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Zusammenfassung: Centrioles and cilia are microtubule-based structures, whose precise formation requires controlled cytoplasmic tubulin incorporation. How cytoplasmic tubulin is recognized for centriolar/ciliary-microtubule construction remains poorly understood. Centrosomal-P4.1-associated-protein (CPAP) binds tubulin via its PN2-3 domain. Here, we show that a C-terminal loop-helix in PN2-3 targets β-tubulin at the microtubule outer surface, while an N-terminal helical motif caps microtubule's α-β surface of β-tubulin. Through this, PN2-3 forms a high-affinity complex with GTP-tubulin, crucial for defining numbers and lengths of centriolar/ciliary-microtubules. Surprisingly, two distinct mutations in PN2-3 exhibit opposite effects on centriolar/ciliary-microtubule lengths. CPAP(F375A), with strongly reduced tubulin interaction, causes shorter centrioles and cilia exhibiting doublet- instead of triplet-microtubules. CPAP(EE343RR) that unmasks the β-tubulin polymerization surface displays slightly reduced tubulin-binding affinity inducing over-elongation of newly forming centriolar/ciliary-microtubules by enhanced dynamic release of its bound tubulin. Thus CPAP regulates delivery of its bound-tubulin to define the size of microtubule-based cellular structures using a 'clutch-like' mechanism.

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 Datum: 2016
 Publikationsstatus: Erschienen
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 Identifikatoren: eDoc: 732378
Anderer: 6585
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Titel: Nature Communications
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 7 Artikelnummer: 11874 Start- / Endseite: - Identifikator: -