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DOI 10.1016/j.ajhg.2013.06.007

Медицинская библиотека · American journal of human genetics · 2013

ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6.

Zariwala Maimoona A, Gee Heon Yung, Kurkowiak Małgorzata, Al-Mutairi Dalal A, Leigh Margaret W, Hurd Toby W, Hjeij Rim, Dell Sharon D, Chaki Moumita, Dougherty Gerard W, Adan Mohamed, Spear Philip C, Esteve-Rudd Julian, Loges Niki T, Rosenfeld Margaret, Diaz Katrina A, Olbrich Heike, Wolf Whitney E, Sheridan Eamonn, Batten Trevor F C, Halbritter Jan, Porath Jonathan D, Kohl Stefan, Lovric Svjetlana, Hwang Daw-Yang, Pittman Jessica E, Burns Kimberlie A, Ferkol Thomas W, Sagel Scott D, Olivier Kenneth N, Morgan Lucy C, Werner Claudius, Raidt Johanna, Pennekamp Petra, Sun Zhaoxia, Zhou Weibin, Airik Rannar, Natarajan Sivakumar, Allen Susan J, Amirav Israel, Wieczorek Dagmar, Landwehr Kerstin, Nielsen Kim, Schwerk Nicolaus, Sertic Jadranka, Köhler Gabriele, Washburn Joseph, Levy Shawn, Fan Shuling, Koerner-Rettberg Cordula, Amselem Serge, Williams David S, Mitchell Brian J, Drummond Iain A, Otto Edgar A, Omran Heymut, Knowles Michael R, Hildebrandt Friedhelm

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.

Для цитирования: Zariwala Maimoona A, Gee Heon Yung, Kurkowiak Małgorzata, Al-Mutairi Dalal A, Leigh Margaret W, Hurd Toby W, Hjeij Rim, Dell Sharon D, Chaki Moumita, Dougherty Gerard W, Adan Mohamed, Spear Philip C, Esteve-Rudd Julian, Loges Niki T, Rosenfeld Margaret, Diaz Katrina A, Olbrich Heike, Wolf Whitney E, Sheridan Eamonn, Batten Trevor F C, Halbritter Jan, Porath Jonathan D, Kohl Stefan, Lovric Svjetlana, Hwang Daw-Yang, Pittman Jessica E, Burns Kimberlie A, Ferkol Thomas W, Sagel Scott D, Olivier Kenneth N, Morgan Lucy C, Werner Claudius, Raidt Johanna, Pennekamp Petra, Sun Zhaoxia, Zhou Weibin, Airik Rannar, Natarajan Sivakumar, Allen Susan J, Amirav Israel, Wieczorek Dagmar, Landwehr Kerstin, Nielsen Kim, Schwerk Nicolaus, Sertic Jadranka, Köhler Gabriele, Washburn Joseph, Levy Shawn, Fan Shuling, Koerner-Rettberg Cordula, Amselem Serge, Williams David S, Mitchell Brian J, Drummond Iain A, Otto Edgar A, Omran Heymut, Knowles Michael R, Hildebrandt Friedhelm. ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6.. American journal of human genetics. 2013. DOI: 10.1016/j.ajhg.2013.06.007.

Предметные рубрики MeSH

AnimalsAutoantigensAxonemal DyneinsBiomarkersCell Cycle ProteinsCiliaCytoskeletal ProteinsExomeGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansKartagener SyndromeMaleMicrotubule-Associated ProteinsMutationPedigreeProtein BindingProtein Structure, TertiaryProteinsRatsRespiratory SystemTumor Suppressor ProteinsXenopus laevisZebrafish
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