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Zheng, X.* ; Ramani, A.* ; Soni, K. ; Gottardo, M.* ; Zheng, S.* ; Gooi, L.M.* ; Li, W.* ; Feng, S.* ; Mariappan, A.* ; Wason, A.* ; Widlund, P.* ; Pozniakovsky, A.* ; Poser, I.* ; Deng, H.* ; Ou, G.* ; Riparbelli, M.* ; Giuliano, C.* ; Hyman, A.A.* ; Sattler, M. ; Gopalakrishnan, J.* ; Li, H.*

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

Nat. Commun. 7:11874 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Microtubule Plus-end; Protein; Centrosome; Dynamics; Cilium; Cells; Identification; Ciliogenesis; Replacement; Transport
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 11874 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed