Cargando…

Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle

Since the discovery of γ-tubulin, attention has focused on its involvement as a microtubule nucleator at the centrosome. However, mislocalization of γ-tubulin away from the centrosome does not inhibit mitotic spindle formation in Drosophila melanogaster, suggesting that a critical function for γ-tub...

Descripción completa

Detalles Bibliográficos
Autores principales: Goshima, Gohta, Mayer, Mirjam, Zhang, Nan, Stuurman, Nico, Vale, Ronald D.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364697/
https://www.ncbi.nlm.nih.gov/pubmed/18443220
http://dx.doi.org/10.1083/jcb.200711053
_version_ 1782154011715043328
author Goshima, Gohta
Mayer, Mirjam
Zhang, Nan
Stuurman, Nico
Vale, Ronald D.
author_facet Goshima, Gohta
Mayer, Mirjam
Zhang, Nan
Stuurman, Nico
Vale, Ronald D.
author_sort Goshima, Gohta
collection PubMed
description Since the discovery of γ-tubulin, attention has focused on its involvement as a microtubule nucleator at the centrosome. However, mislocalization of γ-tubulin away from the centrosome does not inhibit mitotic spindle formation in Drosophila melanogaster, suggesting that a critical function for γ-tubulin might reside elsewhere. A previous RNA interference (RNAi) screen identified five genes (Dgt2–6) required for localizing γ-tubulin to spindle microtubules. We show that the Dgt proteins interact, forming a stable complex. We find that spindle microtubule generation is substantially reduced after knockdown of each Dgt protein by RNAi. Thus, the Dgt complex that we name “augmin” functions to increase microtubule number. Reduced spindle microtubule generation after augmin RNAi, particularly in the absence of functional centrosomes, has dramatic consequences on mitotic spindle formation and function, leading to reduced kinetochore fiber formation, chromosome misalignment, and spindle bipolarity defects. We also identify a functional human homologue of Dgt6. Our results suggest that an important mitotic function for γ-tubulin may lie within the spindle, where augmin and γ-tubulin function cooperatively to amplify the number of microtubules.
format Text
id pubmed-2364697
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-23646972008-11-05 Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle Goshima, Gohta Mayer, Mirjam Zhang, Nan Stuurman, Nico Vale, Ronald D. J Cell Biol Research Articles Since the discovery of γ-tubulin, attention has focused on its involvement as a microtubule nucleator at the centrosome. However, mislocalization of γ-tubulin away from the centrosome does not inhibit mitotic spindle formation in Drosophila melanogaster, suggesting that a critical function for γ-tubulin might reside elsewhere. A previous RNA interference (RNAi) screen identified five genes (Dgt2–6) required for localizing γ-tubulin to spindle microtubules. We show that the Dgt proteins interact, forming a stable complex. We find that spindle microtubule generation is substantially reduced after knockdown of each Dgt protein by RNAi. Thus, the Dgt complex that we name “augmin” functions to increase microtubule number. Reduced spindle microtubule generation after augmin RNAi, particularly in the absence of functional centrosomes, has dramatic consequences on mitotic spindle formation and function, leading to reduced kinetochore fiber formation, chromosome misalignment, and spindle bipolarity defects. We also identify a functional human homologue of Dgt6. Our results suggest that an important mitotic function for γ-tubulin may lie within the spindle, where augmin and γ-tubulin function cooperatively to amplify the number of microtubules. The Rockefeller University Press 2008-05-05 /pmc/articles/PMC2364697/ /pubmed/18443220 http://dx.doi.org/10.1083/jcb.200711053 Text en © 2008 Goshima et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Goshima, Gohta
Mayer, Mirjam
Zhang, Nan
Stuurman, Nico
Vale, Ronald D.
Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title_full Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title_fullStr Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title_full_unstemmed Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title_short Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
title_sort augmin: a protein complex required for centrosome-independent microtubule generation within the spindle
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364697/
https://www.ncbi.nlm.nih.gov/pubmed/18443220
http://dx.doi.org/10.1083/jcb.200711053
work_keys_str_mv AT goshimagohta augminaproteincomplexrequiredforcentrosomeindependentmicrotubulegenerationwithinthespindle
AT mayermirjam augminaproteincomplexrequiredforcentrosomeindependentmicrotubulegenerationwithinthespindle
AT zhangnan augminaproteincomplexrequiredforcentrosomeindependentmicrotubulegenerationwithinthespindle
AT stuurmannico augminaproteincomplexrequiredforcentrosomeindependentmicrotubulegenerationwithinthespindle
AT valeronaldd augminaproteincomplexrequiredforcentrosomeindependentmicrotubulegenerationwithinthespindle