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Genes Dev 2009 Sep 01;2317:2046-59. doi: 10.1101/gad.1810409.
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The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation.

Dammermann A , Pemble H , Mitchell BJ , McLeod I , Yates JR , Kintner C , Desai AB , Oegema K .

Centrioles are subcellular organelles composed of a ninefold symmetric microtubule array that perform two important functions: (1) They build centrosomes that organize the microtubule cytoskeleton, and (2) they template cilia, microtubule-based projections with sensory and motile functions. We identified HYLS-1, a widely conserved protein, based on its direct interaction with the core centriolar protein SAS-4. HYLS-1 localization to centrioles requires SAS-4 and, like SAS-4, HYLS-1 is stably incorporated into the outer centriole wall. Unlike SAS-4, HYLS-1 is dispensable for centriole assembly and centrosome function in cell division. Instead, HYLS-1 plays an essential role in cilia formation that is conserved between Caenorhabditis elegans and vertebrates. A single amino acid change in human HYLS1 leads to a perinatal lethal disorder termed hydrolethalus syndrome, and we show that this mutation impairs HYLS-1 function in ciliogenesis. HYLS-1 is required for the apical targeting/anchoring of centrioles at the plasma membrane but not for the intraflagellar transport-dependent extension of the ciliary axoneme. These findings classify hydrolethalus syndrome as a severe human ciliopathy and shed light on the dual functionality of centrioles, defining the first stably incorporated centriolar protein that is not required for centriole assembly but instead confers on centrioles the capacity to initiate ciliogenesis.

PubMed ID: 19656802
PMC ID: PMC2751977
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: hyls1 ift52 ift88 msgn1 pgap6 ppie tjp1 tspan31 tuba4b tubg1
GO keywords: regulation of cilium assembly
Antibodies: Tjp1 Ab1 Tuba4b Ab5 Tubg1 Ab4 hyls1 Ab1
Morpholinos: hyls1 MO1 hyls1 MO2 ift52 MO1 ift88 MO2

Disease Ontology terms: hydrolethalus syndrome

Article Images: [+] show captions
References [+] :
Afzelius, Cilia-related diseases. 2004, Pubmed