Centrosomes are conserved organelles that are essential for accurate cell division and cilium formation. A centrosome consists of a pair of centrioles surrounded by a protein network of pericentriolar material (PCM) that is essential for the centrosome's function. In this study, we show that Sas-4 provides a scaffold for cytoplasmic complexes (named S-CAP), which include CNN, Asl and D-PLP, proteins that are all found in the centrosomes at the vicinity of the centriole. When Sas-4 is absent, nascent procentrioles are unstable and lack PCM, and functional centrosomes are not generated. When Sas-4 is mutated, so that it cannot form S-CAP complexes, centrosomes are present but with dramatically reduced levels of PCM. Finally, purified S-CAP complexes or recombinant Sas-4 can bind centrosomes stripped of PCM, whereas recombinant CNN or Asl cannot. In summary, PCM assembly begins in the cytosol where Sas-4 provides a scaffold for pre-assembled cytoplasmic complexes before tethering of the complexes in a centrosome.
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http://dx.doi.org/10.1038/ncomms1367 | DOI Listing |
Development
October 2021
Department Biology II, Ludwig-Maximilians-University, Munich, 82152 Planegg-Martinsried, Germany.
Correct cell division relies on the formation of a bipolar spindle. In animal cells, microtubule nucleation at the spindle poles is facilitated by the pericentriolar material (PCM), which assembles around a pair of centrioles. Although centrioles are essential for PCM assembly, the proteins that anchor the PCM to the centrioles are less known.
View Article and Find Full Text PDFNat Commun
April 2020
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
J Cell Sci
February 2018
Department of Life Sciences, Via A. Moro 2, University of Siena, 53100 Siena, Italy
In the developing eye, the centrioles of the differentiating retinal cells are not surrounded by the microtubule-nucleating γ-tubulin, suggesting that they are unable to organize functional microtubule-organizing centers. Consistent with this idea, Cnn and Spd-2, which are involved in γ-tubulin recruitment, and the scaffold protein Plp, which plays a role in the organization of the pericentriolar material, are lost in the third-instar larval stage. However, the centrioles maintain their structural integrity, and both the parent centrioles accumulate Asl and Ana1.
View Article and Find Full Text PDFElife
November 2015
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Centrosomes have many important functions and comprise a 'mother' and 'daughter' centriole surrounded by pericentriolar material (PCM). The mother centriole recruits and organises the PCM and templates the formation of the daughter centriole. It has been reported that several important Drosophila PCM-organising proteins are recruited to centrioles from the cytosol as part of large cytoplasmic 'S-CAP' complexes that contain the centriole protein Sas-4.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2014
Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, and Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, People's Republic of China.
Pericentriolar material (PCM) recruitment to centrioles forms a key step in centrosome biogenesis. Deregulation of this process leads to centrosome aberrations causing disorders, one of which is autosomal recessive primary microcephaly (MCPH), a neurodevelopmental disorder where brain size is reduced. During PCM recruitment, the conserved centrosomal protein Sas-4/CPAP/MCPH6, known to play a role in centriole formation, acts as a scaffold for cytoplasmic PCM complexes to bind and then tethers them to centrioles to form functional centrosomes.
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