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EMBO J. 2015 Apr 15;34(8):1078-89. doi: 10.15252/embj.201490805. Epub 2015 Feb 23.

Cyclin O (Ccno) functions during deuterosome-mediated centriole amplification of multiciliated cells.

Author information

1
University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany Spemann Graduate School of Biology and Medicine, Freiburg, Germany.
2
University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany.
3
Department of Pediatrics, University Hospital Muenster, Muenster, Germany.
4
University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany.
5
Department of Dermatology, ZBSA Centre for Biological Systems Analysis, Medical Centre University of Freiburg, Freiburg, Germany.
6
BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany Department of Dermatology, ZBSA Centre for Biological Systems Analysis, Medical Centre University of Freiburg, Freiburg, Germany.
7
Medical Biology and Electron Microscopy Centre, University Medicine Rostock, Rostock, Germany.
8
University Medical Centre, Renal Department, Centre for Clinical Research, Freiburg, Germany BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany sebastian.arnold@uniklinik-freiburg.de.

Abstract

Mucociliary clearance and fluid transport along epithelial surfaces are carried out by multiciliated cells (MCCs). Recently, human mutations in Cyclin O (CCNO) were linked to severe airway disease. Here, we show that Ccno expression is restricted to MCCs and the genetic deletion of Ccno in mouse leads to reduced numbers of multiple motile cilia and characteristic phenotypes of MCC dysfunction including severe hydrocephalus and mucociliary clearance deficits. Reduced cilia numbers are caused by compromised generation of centrioles at deuterosomes, which serve as major amplification platform for centrioles in MCCs. Ccno-deficient MCCs fail to sufficiently generate deuterosomes, and only reduced numbers of fully functional centrioles that undergo maturation to ciliary basal bodies are formed. Collectively, this study implicates CCNO as first known regulator of deuterosome formation and function for the amplification of centrioles in MCCs.

KEYWORDS:

Ccno; centriole amplification; deuterosomes; mouse; multiciliated cells

PMID:
25712475
PMCID:
PMC4406653
DOI:
10.15252/embj.201490805
[Indexed for MEDLINE]
Free PMC Article

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