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Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry
The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknow...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694761/ https://www.ncbi.nlm.nih.gov/pubmed/26538025 http://dx.doi.org/10.1091/mbc.E15-07-0474 |
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author | Silva, Erica Betleja, Ewelina John, Emily Spear, Philip Moresco, James J. Zhang, Siwei Yates, John R. Mitchell, Brian J. Mahjoub, Moe R. |
author_facet | Silva, Erica Betleja, Ewelina John, Emily Spear, Philip Moresco, James J. Zhang, Siwei Yates, John R. Mitchell, Brian J. Mahjoub, Moe R. |
author_sort | Silva, Erica |
collection | PubMed |
description | The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites—cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer’s vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite–associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease. |
format | Online Article Text |
id | pubmed-4694761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46947612016-03-16 Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry Silva, Erica Betleja, Ewelina John, Emily Spear, Philip Moresco, James J. Zhang, Siwei Yates, John R. Mitchell, Brian J. Mahjoub, Moe R. Mol Biol Cell Articles The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites—cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer’s vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite–associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease. The American Society for Cell Biology 2016-01-01 /pmc/articles/PMC4694761/ /pubmed/26538025 http://dx.doi.org/10.1091/mbc.E15-07-0474 Text en © 2016 Silva, Betleja, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Silva, Erica Betleja, Ewelina John, Emily Spear, Philip Moresco, James J. Zhang, Siwei Yates, John R. Mitchell, Brian J. Mahjoub, Moe R. Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title | Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title_full | Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title_fullStr | Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title_full_unstemmed | Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title_short | Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
title_sort | ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694761/ https://www.ncbi.nlm.nih.gov/pubmed/26538025 http://dx.doi.org/10.1091/mbc.E15-07-0474 |
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