Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome

Hydrolethalus syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. How HYLS1 controls centriole function 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 HLS. These phenotypes arise from a loss of centriole integrity that causes tissue-specific defects in cilia assembly and function. We show that HYLS1 is recruited to the centriole by CEP120 and stabilizes the localization of centriole inner scaffold proteins that ensure the integrity of the centriolar microtubule wall. The HLS disease mutation reduced the centriole localization of HYLS1 and caused degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and contribute to HLS phenotypes.

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Publication Details

Journal
The Journal of Cell Biology
Published
2025-01-22
DOI
https://doi.org/10.1083/jcb.202403022
Citations
4
Primary Topic
Genetic and Kidney Cyst Diseases
Type
article
Field-Weighted Citation Impact
7.27

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article

Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome

Andrew J. Holland, Margaret A. Strong, Ana Curinha, Thao P. Phan et al.
4 citations
The Journal of Cell Biology
Genetic and Kidney Cyst Diseases
7.27
article

Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome

Andrew J. Holland, Margaret A. Strong, Ana Curinha, Thao P. Phan, Cayla E Jewett, Colin R. Gliech, Taylor Anglen, Anoek Friskes, Zhaoyu Huang, Zachary Nicholas
article en
4 citations

Abstract

Hydrolethalus syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. How HYLS1 controls centriole function 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 HLS. These phenotypes arise from a loss of centriole integrity that causes tissue-specific defects in cilia assembly and function. We show that HYLS1 is recruited to the centriole by CEP120 and stabilizes the localization of centriole inner scaffold proteins that ensure the integrity of the centriolar microtubule wall. The HLS disease mutation reduced the centriole localization of HYLS1 and caused degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and contribute to HLS phenotypes.

The Journal of Cell BiologyVol. 224(4)
Johns Hopkins University (US), Duke University (US), University of California, San Francisco (US), Johns Hopkins Medicine (US), The Netherlands Cancer Institute (NL), Oncode Institute (NL)
Damon Runyon Cancer Research Foundation, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 4%
Genetic and Kidney Cyst Diseases
7.27
DOIOpen Access PDFOpenAlex
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