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Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation

Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. Here, we show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteabl...

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Autores principales: Zhang, Yingjie, Rai, Madhulika, Wang, Cheng, Gonzalez, Cayetano, Wang, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812327/
https://www.ncbi.nlm.nih.gov/pubmed/27025979
http://dx.doi.org/10.1038/srep23735
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author Zhang, Yingjie
Rai, Madhulika
Wang, Cheng
Gonzalez, Cayetano
Wang, Hongyan
author_facet Zhang, Yingjie
Rai, Madhulika
Wang, Cheng
Gonzalez, Cayetano
Wang, Hongyan
author_sort Zhang, Yingjie
collection PubMed
description Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. Here, we show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with severe neuroblast overgrowth, despite that Pins depletion alone results in smaller brains with partially disrupted neuroblast polarity. We show that Prefoldin acts synergistically with Pins to regulate asymmetric division of both neuroblasts and Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α-tubulin or β-tubulin in pins(-) mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins double mutant brains. Our data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells.
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spelling pubmed-48123272016-04-04 Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation Zhang, Yingjie Rai, Madhulika Wang, Cheng Gonzalez, Cayetano Wang, Hongyan Sci Rep Article Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. Here, we show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with severe neuroblast overgrowth, despite that Pins depletion alone results in smaller brains with partially disrupted neuroblast polarity. We show that Prefoldin acts synergistically with Pins to regulate asymmetric division of both neuroblasts and Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α-tubulin or β-tubulin in pins(-) mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins double mutant brains. Our data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells. Nature Publishing Group 2016-03-30 /pmc/articles/PMC4812327/ /pubmed/27025979 http://dx.doi.org/10.1038/srep23735 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Yingjie
Rai, Madhulika
Wang, Cheng
Gonzalez, Cayetano
Wang, Hongyan
Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title_full Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title_fullStr Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title_full_unstemmed Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title_short Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation
title_sort prefoldin and pins synergistically regulate asymmetric division and suppress dedifferentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812327/
https://www.ncbi.nlm.nih.gov/pubmed/27025979
http://dx.doi.org/10.1038/srep23735
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