Actin-dependent regulation of cilia length by the inverted formin FHDC1
| Autor: | John W. Copeland, Andrea McRae, Giulia Guarguaglini, Laura Trinkle-Mulcahy, Sarah J. Copeland |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Fetal Proteins
0301 basic medicine Formins Golgi Apparatus Cep170 Biology Mice 03 medical and health sciences 0302 clinical medicine citoscheletro Microtubule Ciliogenesis Animals Cilia Cytoskeleton Molecular Biology Actin Centrioles formina FHDC1 Cilium Microfilament Proteins Nuclear Proteins Cell Biology respiratory system CEP170 Actins Cell biology 030104 developmental biology ciliogenesi Cytoplasm NIH 3T3 Cells biology.protein 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular biology of the cell 29 (2018): 1611–1627. doi:10.1091/mbc.E18-02-0088 info:cnr-pdr/source/autori:Copeland S.J.; McRae A.; Guarguaglini G.; Trinkle-Mulcahy L.; Copeland J.W./titolo:Actin-dependent regulation of cilia length by the inverted formin FHDC1/doi:10.1091%2Fmbc.E18-02-0088/rivista:Molecular biology of the cell/anno:2018/pagina_da:1611/pagina_a:1627/intervallo_pagine:1611–1627/volume:29 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e18-02-0088 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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