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A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth

ABSTRACT: Cilia are essential motile or sensory organelles found on many eukaryotic cells. Their formation and function rely on axonemal microtubules, which exhibit very slow dynamics, however the underlying biochemical mechanisms are largely unexplored. Here, we reconstituted in vitro the individual and collective activities of the ciliary tip module proteins, CEP104, CSPP1, TOGARAM1, ARMC9 and CCDC66, which interact with each other and with microtubules, and, when mutated, cause ciliopathies such as Joubert syndrome. CEP104, a protein containing a tubulin-binding TOG domain, is an inhibitor of microtubule growth and shortening that interacts with EBs on the microtubule surface and with a luminal microtubule-pausing factor CSPP1. Another TOG-domain protein, TOGARAM1, overcomes growth inhibition imposed by CEP104 and CSPP1. CCDC66 and ARMC9 do not affect microtubule dynamics directly but act as scaffolds for their partners. Cryo-electron tomography showed that together, ciliary tip module members form plus-end-specific cork-like structures which reduce protofilament flaring. The combined effect of these proteins is very slow processive microtubule elongation, which recapitulates axonemal dynamics in cells.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Kelly Stecker

LAB HEAD: Kelly E. Stecker

PROVIDER: PXD055631 | Pride | 2024-11-19

REPOSITORIES: Pride

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			Action	DRS
	20210618_EX1_UM8_ARMC9.raw	Raw
	20210618_EX1_UM8_ARMC9.xlsx	Xlsx
	20210618_EX1_UM8_CEP104.raw	Raw
	20210618_EX1_UM8_CEP104.xlsx	Xlsx
	20210618_EX1_UM8_TOGARAM1.raw	Raw

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A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth

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