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Actin-dependent regulation of cilia length by the inverted formin FHDC1
A primary cilium is found on most mammalian cells, where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis, reflecting the ubiquity of the function of cilia and the number of proteins required for...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080654/ https://www.ncbi.nlm.nih.gov/pubmed/29742020 http://dx.doi.org/10.1091/mbc.E18-02-0088 |
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author | Copeland, Sarah J. McRae, Andrea Guarguaglini, Giulia Trinkle-Mulcahy, Laura Copeland, John W. |
author_facet | Copeland, Sarah J. McRae, Andrea Guarguaglini, Giulia Trinkle-Mulcahy, Laura Copeland, John W. |
author_sort | Copeland, Sarah J. |
collection | PubMed |
description | A primary cilium is found on most mammalian cells, where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis, reflecting the ubiquity of the function of cilia and the number of proteins required for their assembly. Proper cilia length is necessary for cilia signaling and is regulated through a poorly understood balance of assembly and disassembly rates. FHDC1 is a unique member of the formin family of cytoskeletal regulatory proteins. Overexpression of FHDC1 induces F-actin accumulation and microtubule stabilization and acetylation. We find that overexpression of FHDC1 also has profound effects on ciliogenesis; in most cells FHDC1 overexpression blocks cilia assembly, but the cilia that are present are immensely elongated. FHDC1-induced cilia growth requires the FHDC1 FH2 and microtubule-binding domain and results from F-actin–dependent inhibition of cilia disassembly. FHDC1 depletion, or treatment with a pan-formin inhibitor, inhibits cilia assembly and induces cilia resorption. Endogenous FHDC1 protein localizes to cytoplasmic microtubules converging on the base of the cilia, and we identify the subdistal appendage protein Cep170 as an FHDC1 interacting protein. Our results suggest that FHDC1 plays a role in coordinating cytoskeletal dynamics during normal cilia assembly. |
format | Online Article Text |
id | pubmed-6080654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60806542018-09-16 Actin-dependent regulation of cilia length by the inverted formin FHDC1 Copeland, Sarah J. McRae, Andrea Guarguaglini, Giulia Trinkle-Mulcahy, Laura Copeland, John W. Mol Biol Cell Articles A primary cilium is found on most mammalian cells, where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis, reflecting the ubiquity of the function of cilia and the number of proteins required for their assembly. Proper cilia length is necessary for cilia signaling and is regulated through a poorly understood balance of assembly and disassembly rates. FHDC1 is a unique member of the formin family of cytoskeletal regulatory proteins. Overexpression of FHDC1 induces F-actin accumulation and microtubule stabilization and acetylation. We find that overexpression of FHDC1 also has profound effects on ciliogenesis; in most cells FHDC1 overexpression blocks cilia assembly, but the cilia that are present are immensely elongated. FHDC1-induced cilia growth requires the FHDC1 FH2 and microtubule-binding domain and results from F-actin–dependent inhibition of cilia disassembly. FHDC1 depletion, or treatment with a pan-formin inhibitor, inhibits cilia assembly and induces cilia resorption. Endogenous FHDC1 protein localizes to cytoplasmic microtubules converging on the base of the cilia, and we identify the subdistal appendage protein Cep170 as an FHDC1 interacting protein. Our results suggest that FHDC1 plays a role in coordinating cytoskeletal dynamics during normal cilia assembly. The American Society for Cell Biology 2018-07-01 /pmc/articles/PMC6080654/ /pubmed/29742020 http://dx.doi.org/10.1091/mbc.E18-02-0088 Text en © 2018 Copeland et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Copeland, Sarah J. McRae, Andrea Guarguaglini, Giulia Trinkle-Mulcahy, Laura Copeland, John W. Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title | Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title_full | Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title_fullStr | Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title_full_unstemmed | Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title_short | Actin-dependent regulation of cilia length by the inverted formin FHDC1 |
title_sort | actin-dependent regulation of cilia length by the inverted formin fhdc1 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080654/ https://www.ncbi.nlm.nih.gov/pubmed/29742020 http://dx.doi.org/10.1091/mbc.E18-02-0088 |
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