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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...

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Autores principales: Copeland, Sarah J., McRae, Andrea, Guarguaglini, Giulia, Trinkle-Mulcahy, Laura, Copeland, John W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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.
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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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