Universität zu Köln

Zheng, Xiangdong, Ramani, Anand, Soni, Komal, Gottardo, Marco ORCID: 0000-0001-8649-7799, Zheng, Shuangping, Gooi, Li Ming, Li, Wenjing, Feng, Shan, Mariappan, Aruljothi, Wason, Arpit, Widlund, Per ORCID: 0000-0002-3645-0009, Pozniakovsky, Andrei, Poser, Ina, Deng, Haiteng ORCID: 0000-0001-9496-1280, Ou, Guangshuo, Riparbelli, Maria, Giuliano, Callaini, Hyman, Anthony A., Sattler, Michael ORCID: 0000-0002-1594-0527, Gopalakrishnan, Jay and Li, Haitao ORCID: 0000-0001-6741-293X (2016). Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length. Nat. Commun., 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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 beta-tubulin at the microtubule outer surface, while an N-terminal helical motif caps microtubule's alpha-beta surface of beta-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 beta-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zheng, Xiangdong UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramani, Anand UNSPECIFIED UNSPECIFIED UNSPECIFIED Soni, Komal UNSPECIFIED UNSPECIFIED UNSPECIFIED Gottardo, Marco UNSPECIFIED orcid.org/0000-0001-8649-7799 UNSPECIFIED Zheng, Shuangping UNSPECIFIED UNSPECIFIED UNSPECIFIED Gooi, Li Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Wenjing UNSPECIFIED UNSPECIFIED UNSPECIFIED Feng, Shan UNSPECIFIED UNSPECIFIED UNSPECIFIED Mariappan, Aruljothi UNSPECIFIED UNSPECIFIED UNSPECIFIED Wason, Arpit UNSPECIFIED UNSPECIFIED UNSPECIFIED Widlund, Per UNSPECIFIED orcid.org/0000-0002-3645-0009 UNSPECIFIED Pozniakovsky, Andrei UNSPECIFIED UNSPECIFIED UNSPECIFIED Poser, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Deng, Haiteng UNSPECIFIED orcid.org/0000-0001-9496-1280 UNSPECIFIED Ou, Guangshuo UNSPECIFIED UNSPECIFIED UNSPECIFIED Riparbelli, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Giuliano, Callaini UNSPECIFIED UNSPECIFIED UNSPECIFIED Hyman, Anthony A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sattler, Michael UNSPECIFIED orcid.org/0000-0002-1594-0527 UNSPECIFIED Gopalakrishnan, Jay UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Haitao UNSPECIFIED orcid.org/0000-0001-6741-293X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-274757
DOI:	10.1038/ncomms11874
Journal or Publication Title:	Nat. Commun.
Volume:	7
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MICROTUBULE; PROTEIN; IDENTIFICATION; TRANSPORT; DYNAMICS; CILIUM; SYSTEM; SAS-4 Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27475