Zheng, Xiangdong, Gooi, Li Ming, Wason, Arpit, Gabriel, Elke, Mehrjardi, Narges Zare, Yang, Qian, Zhang, Xingrun, Debec, Alain, Basiri, Marcus L., Avidor-Reiss, Tomer ORCID: 0000-0003-0918-526X, Pozniakovsky, Andrei, Poser, Ina, Saric, Tomo ORCID: 0000-0001-8344-1095, Hyman, Anthony A., Li, Haitao ORCID: 0000-0001-6741-293X and Gopalakrishnan, Jay (2014). Conserved TCP domain of Sas-4/CPAP is essential for pericentriolar material tethering during centrosome biogenesis. Proc. Natl. Acad. Sci. U. S. A., 111 (3). S. E354 - 10. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

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 neuro-developmental 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. To understand Sas-4's tethering role, we determined the crystal structure of its T complex protein 10 (TCP) domain displaying a solvent-exposed single-layer of beta-sheets fold. This unique feature of the TCP domain suggests that it could provide an extended surface-like platform to tether the Sas-4-PCM scaffold to a centriole. Functional studies in Drosophila, human cells, and human induced pluripotent stem cell-derived neural progenitor cells were used to test this hypothesis, where point mutations within the 9-10th beta-strands (beta 9-10 mutants including a MCPH-associated mutation) perturbed PCM tethering while allowing Sas-4/CPAP to scaffold cytoplasmic PCM complexes. Specifically, the Sas-4 beta 9-10 mutants displayed perturbed interactions with Ana2, a centrosome duplication factor, and Bld-10, a centriole microtubule-binding protein, suggesting a role for the beta 9-10 surface in mediating protein-protein interactions for efficient Sas4-PCM scaffold centriole tethering. Hence, we provide possible insights into how centrosomal protein defects result in human MCPH and how Sas-4 proteins act as a vehicle to tether PCM complexes to centrioles independent of its well-known role in centriole duplication.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zheng, XiangdongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gooi, Li MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wason, ArpitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabriel, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehrjardi, Narges ZareUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, QianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, XingrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Debec, AlainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Basiri, Marcus L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avidor-Reiss, TomerUNSPECIFIEDorcid.org/0000-0003-0918-526XUNSPECIFIED
Pozniakovsky, AndreiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poser, InaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saric, TomoUNSPECIFIEDorcid.org/0000-0001-8344-1095UNSPECIFIED
Hyman, Anthony A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, HaitaoUNSPECIFIEDorcid.org/0000-0001-6741-293XUNSPECIFIED
Gopalakrishnan, JayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-448348
DOI: 10.1073/pnas.1317535111
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 111
Number: 3
Page Range: S. E354 - 10
Date: 2014
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HUMAN-CELLS; CENTRIOLE DUPLICATION; HYDROPHOBIC CORE; PROTEIN CPAP; STIL; ARCHITECTURE; NUCLEATION; COMPLEXES; ASTERLESS; INTERACTSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44834

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