Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Silva, Erica, Betleja, Ewelina, John, Emily, Spear, Philip, Moresco, James J., Zhang, Siwei, Yates, John R., Mitchell, Brian J., Mahjoub, Moe R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
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
_version_ 1782407516434464768
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
work_keys_str_mv AT silvaerica ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT betlejaewelina ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT johnemily ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT spearphilip ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT morescojamesj ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT zhangsiwei ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT yatesjohnr ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT mitchellbrianj ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry
AT mahjoubmoer ccdc11isanovelcentriolarsatelliteproteinessentialforciliogenesisandestablishmentofleftrightasymmetry