Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Zheng, Xiangdong UNSPECIFIED UNSPECIFIED UNSPECIFIED Gooi, Li Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Wason, Arpit UNSPECIFIED UNSPECIFIED UNSPECIFIED Gabriel, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehrjardi, Narges Zare UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Qian UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Xingrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Debec, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED Basiri, Marcus L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Avidor-Reiss, Tomer UNSPECIFIED orcid.org/0000-0003-0918-526X UNSPECIFIED Pozniakovsky, Andrei UNSPECIFIED UNSPECIFIED UNSPECIFIED Poser, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Saric, Tomo UNSPECIFIED orcid.org/0000-0001-8344-1095 UNSPECIFIED Hyman, Anthony A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Haitao UNSPECIFIED orcid.org/0000-0001-6741-293X UNSPECIFIED Gopalakrishnan, Jay UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language HUMAN-CELLS; CENTRIOLE DUPLICATION; HYDROPHOBIC CORE; PROTEIN CPAP; STIL; ARCHITECTURE; NUCLEATION; COMPLEXES; ASTERLESS; INTERACTS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44834