Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome.

Autor:	Curinha A; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Huang Z; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Anglen T; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Strong MA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Gliech CR; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Jewett CE; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Friskes A; Division of Cell Biology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Holland AJ; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 06. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1101/2024.03.06.583733
Abstrakt:	Hydrolethalus Syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. However, how HYLS1 facilitates the centriole-based templating of cilia is poorly understood. Here, we show that mice harboring the HYLS1 disease mutation die shortly after birth and exhibit developmental defects that recapitulate several manifestations of the human disease. These phenotypes arise from tissue-specific defects in cilia assembly and function caused by a loss of centriole integrity. We show that HYLS1 is recruited to the centriole by CEP120 and functions to recruit centriole inner scaffold proteins that stabilize the centriolar microtubule wall. The HLS mutation disrupts the interaction of HYLS1 with CEP120 leading to HYLS1 displacement and degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and drive HLS phenotypes. Competing Interests: COMPETING INTERESTS: The Authors declare that they have no competing interests.
Databáze:	MEDLINE
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