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

Xiangdong Zheng, Anand Ramani, Komal Soni, Marco Gottardo, Shuangping Zheng, Li Ming Gooi, Wenjing Li, Shan Feng, Aruljothi Mariappan, Arpit Wason, Per Widlund, Andrei Pozniakovsky, Ina Poser, Haiteng Deng, Guangshuo Ou, Maria Riparbelli, Callaini Giuliano, Anthony A. Hyman, Michael Sattler, Jay Gopalakrishnan () and Haitao Li ()
Additional contact information
Xiangdong Zheng: Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University
Anand Ramani: Institute for Biochemistry I and Center for Molecular Medicine of the University of Cologne
Komal Soni: Institute of Structural Biology, Helmholtz Zentrum München
Marco Gottardo: University of Siena
Shuangping Zheng: Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University
Li Ming Gooi: Institute for Biochemistry I and Center for Molecular Medicine of the University of Cologne
Wenjing Li: MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University
Shan Feng: MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University
Aruljothi Mariappan: Institute for Biochemistry I and Center for Molecular Medicine of the University of Cologne
Arpit Wason: Institute for Biochemistry I and Center for Molecular Medicine of the University of Cologne
Per Widlund: Max Planck Institute of Molecular Cell Biology and Genetics
Andrei Pozniakovsky: Max Planck Institute of Molecular Cell Biology and Genetics
Ina Poser: Max Planck Institute of Molecular Cell Biology and Genetics
Haiteng Deng: MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University
Guangshuo Ou: MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University
Maria Riparbelli: University of Siena
Callaini Giuliano: University of Siena
Anthony A. Hyman: Max Planck Institute of Molecular Cell Biology and Genetics
Michael Sattler: Institute of Structural Biology, Helmholtz Zentrum München
Jay Gopalakrishnan: Institute for Biochemistry I and Center for Molecular Medicine of the University of Cologne
Haitao Li: Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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. CPAPF375A, with strongly reduced tubulin interaction, causes shorter centrioles and cilia exhibiting doublet- instead of triplet-microtubules. CPAPEE343RR 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.

Date: 2016
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DOI: 10.1038/ncomms11874

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