Overly long centrioles and defective cell division upon excess of the SAS-4-related protein CPAP.
The centrosome is the principal microtubule organizing center (MTOC) of animal cells. Accurate centrosome duplication is fundamental for genome integrity and entails the formation of one procentriole next to each existing centriole, once per cell cycle. The procentriole then elongates to eventually reach the same size as the centriole. The mechanisms that govern elongation of the centriolar cylinder and their potential relevance for cell division are not known. Here, we show that the SAS-4-related protein CPAP is required for centrosome duplication in cycling human cells. Furthermore, we demonstrate that CPAP overexpression results in the formation of abnormally long centrioles. This also promotes formation of more than one procentriole in the vicinity of such overly long centrioles, eventually resulting in the presence of supernumerary MTOCs. This in turn leads to multipolar spindle assembly and cytokinesis defects. Overall, our findings suggest that centriole length must be carefully regulated to restrict procentriole number and thus ensure accurate cell division.
Kohlmaier
Gregor
G
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Loncarek
Jadranka
J
Meng
Xing
X
McEwen
Bruce F
BF
Mogensen
Mette M
MM
Spektor
Alexander
A
Dynlacht
Brian D
BD
Khodjakov
Alexey
A
Gönczy
Pierre
P
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
C414735:CENPJ protein, human; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins