Cargando…

Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly

Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the cen...

Descripción completa

Detalles Bibliográficos
Autores principales: Hori, Akiko, Peddie, Christopher J., Collinson, Lucy M., Toda, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472012/
https://www.ncbi.nlm.nih.gov/pubmed/25833712
http://dx.doi.org/10.1091/mbc.E14-11-1561
_version_ 1782376991162368000
author Hori, Akiko
Peddie, Christopher J.
Collinson, Lucy M.
Toda, Takashi
author_facet Hori, Akiko
Peddie, Christopher J.
Collinson, Lucy M.
Toda, Takashi
author_sort Hori, Akiko
collection PubMed
description Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the centrosome is unknown. hMsd1/SSX2IP localizes to both the centrosome and centriolar satellites and is required for tethering microtubules to the centrosome. Here we show that hMsd1/SSX2IP-mediated microtubule anchoring is essential for proper centriole assembly and duplication. On hMsd1/SSX2IP knockdown, the centriolar satellites become stuck at the microtubule minus end near the centrosome. Intriguingly, these satellites contain many proteins that normally localize to the centrosome. Of importance, microtubule structures, albeit not being anchored properly, are still required for the emergence of abnormal satellites, as complete microtubule depolymerization results in the disappearance of these aggregates from the vicinity of the centrosome. We highlighted, using superresolution and electron microscopy, that under these conditions, centriole structures are faulty. Remarkably, these cells are insensitive to Plk4 overproduction–induced ectopic centriole formation, yet they accelerate centrosome reduplication upon hydroxyurea arrest. Finally, the appearance of satellite aggregates is cancer cell specific. Together our findings provide novel insights into the mechanism of centriole assembly and microtubule anchoring.
format Online
Article
Text
id pubmed-4472012
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-44720122015-08-16 Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly Hori, Akiko Peddie, Christopher J. Collinson, Lucy M. Toda, Takashi Mol Biol Cell Articles Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the centrosome is unknown. hMsd1/SSX2IP localizes to both the centrosome and centriolar satellites and is required for tethering microtubules to the centrosome. Here we show that hMsd1/SSX2IP-mediated microtubule anchoring is essential for proper centriole assembly and duplication. On hMsd1/SSX2IP knockdown, the centriolar satellites become stuck at the microtubule minus end near the centrosome. Intriguingly, these satellites contain many proteins that normally localize to the centrosome. Of importance, microtubule structures, albeit not being anchored properly, are still required for the emergence of abnormal satellites, as complete microtubule depolymerization results in the disappearance of these aggregates from the vicinity of the centrosome. We highlighted, using superresolution and electron microscopy, that under these conditions, centriole structures are faulty. Remarkably, these cells are insensitive to Plk4 overproduction–induced ectopic centriole formation, yet they accelerate centrosome reduplication upon hydroxyurea arrest. Finally, the appearance of satellite aggregates is cancer cell specific. Together our findings provide novel insights into the mechanism of centriole assembly and microtubule anchoring. The American Society for Cell Biology 2015-06-01 /pmc/articles/PMC4472012/ /pubmed/25833712 http://dx.doi.org/10.1091/mbc.E14-11-1561 Text en © 2015 Hori 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
Hori, Akiko
Peddie, Christopher J.
Collinson, Lucy M.
Toda, Takashi
Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title_full Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title_fullStr Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title_full_unstemmed Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title_short Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly
title_sort centriolar satellite– and hmsd1/ssx2ip-dependent microtubule anchoring is critical for centriole assembly
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472012/
https://www.ncbi.nlm.nih.gov/pubmed/25833712
http://dx.doi.org/10.1091/mbc.E14-11-1561
work_keys_str_mv AT horiakiko centriolarsatelliteandhmsd1ssx2ipdependentmicrotubuleanchoringiscriticalforcentrioleassembly
AT peddiechristopherj centriolarsatelliteandhmsd1ssx2ipdependentmicrotubuleanchoringiscriticalforcentrioleassembly
AT collinsonlucym centriolarsatelliteandhmsd1ssx2ipdependentmicrotubuleanchoringiscriticalforcentrioleassembly
AT todatakashi centriolarsatelliteandhmsd1ssx2ipdependentmicrotubuleanchoringiscriticalforcentrioleassembly