| Structural highlights
Function
[CE120_MOUSE] Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis.[1] [2] [3]
Publication Abstract from PubMed
Ciliopathies are a group of genetic disorders caused by a failure to form functional cilia. Due to a lack of structural information, it is currently poorly understood how ciliopathic mutations affect protein functionality to give rise to the underlying disease. Using X-ray crystallography, we show that the ciliopathy-associated centriolar protein CEP120 contains three C2 domains. The point mutations V194A and A199P, which cause Joubert syndrome (JS) and Jeune asphyxiating thoracic dystrophy (JATD), respectively, both reduce the thermostability of the second C2 domain by targeting residues that point toward its hydrophobic core. Genome-engineered cells homozygous for these mutations have largely normal centriole numbers but show reduced CEP120 levels, compromised recruitment of distal centriole markers, and deficient cilia formation. Our results provide insight into the disease mechanism of two ciliopathic mutations in CEP120, identify putative binding partners of CEP120 C2B, and suggest a complex genotype-phenotype relation of the CEP120 ciliopathy alleles.
Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis.,Joseph N, Al-Jassar C, Johnson CM, Andreeva A, Barnabas DD, Freund SMV, Gergely F, van Breugel M Cell Rep. 2018 May 29;23(9):2805-2818. doi: 10.1016/j.celrep.2018.04.100. PMID:29847808[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xie Z, Moy LY, Sanada K, Zhou Y, Buchman JJ, Tsai LH. Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron. 2007 Oct 4;56(1):79-93. PMID:17920017 doi:http://dx.doi.org/10.1016/j.neuron.2007.08.026
- ↑ Hutchins JR, Toyoda Y, Hegemann B, Poser I, Heriche JK, Sykora MM, Augsburg M, Hudecz O, Buschhorn BA, Bulkescher J, Conrad C, Comartin D, Schleiffer A, Sarov M, Pozniakovsky A, Slabicki MM, Schloissnig S, Steinmacher I, Leuschner M, Ssykor A, Lawo S, Pelletier L, Stark H, Nasmyth K, Ellenberg J, Durbin R, Buchholz F, Mechtler K, Hyman AA, Peters JM. Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science. 2010 Apr 30;328(5978):593-9. doi: 10.1126/science.1181348. Epub 2010 Apr, 1. PMID:20360068 doi:http://dx.doi.org/10.1126/science.1181348
- ↑ Wu C, Yang M, Li J, Wang C, Cao T, Tao K, Wang B. Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors. PLoS One. 2014 Sep 24;9(9):e107943. doi: 10.1371/journal.pone.0107943., eCollection 2014. PMID:25251415 doi:http://dx.doi.org/10.1371/journal.pone.0107943
- ↑ Joseph N, Al-Jassar C, Johnson CM, Andreeva A, Barnabas DD, Freund SMV, Gergely F, van Breugel M. Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis. Cell Rep. 2018 May 29;23(9):2805-2818. doi: 10.1016/j.celrep.2018.04.100. PMID:29847808 doi:http://dx.doi.org/10.1016/j.celrep.2018.04.100
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