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Delineation of proteome changes driven by cell size and growth rate

Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cel...

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Autores principales: Zatulovskiy, Evgeny, Lanz, Michael C., Zhang, Shuyuan, McCarthy, Frank, Elias, Joshua E., Skotheim, Jan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483106/
https://www.ncbi.nlm.nih.gov/pubmed/36133920
http://dx.doi.org/10.3389/fcell.2022.980721
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author Zatulovskiy, Evgeny
Lanz, Michael C.
Zhang, Shuyuan
McCarthy, Frank
Elias, Joshua E.
Skotheim, Jan M.
author_facet Zatulovskiy, Evgeny
Lanz, Michael C.
Zhang, Shuyuan
McCarthy, Frank
Elias, Joshua E.
Skotheim, Jan M.
author_sort Zatulovskiy, Evgeny
collection PubMed
description Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell’s proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell’s declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell’s growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology.
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spelling pubmed-94831062022-09-20 Delineation of proteome changes driven by cell size and growth rate Zatulovskiy, Evgeny Lanz, Michael C. Zhang, Shuyuan McCarthy, Frank Elias, Joshua E. Skotheim, Jan M. Front Cell Dev Biol Cell and Developmental Biology Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell’s proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell’s declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell’s growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology. Frontiers Media S.A. 2022-09-05 /pmc/articles/PMC9483106/ /pubmed/36133920 http://dx.doi.org/10.3389/fcell.2022.980721 Text en Copyright © 2022 Zatulovskiy, Lanz, Zhang, McCarthy, Elias and Skotheim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zatulovskiy, Evgeny
Lanz, Michael C.
Zhang, Shuyuan
McCarthy, Frank
Elias, Joshua E.
Skotheim, Jan M.
Delineation of proteome changes driven by cell size and growth rate
title Delineation of proteome changes driven by cell size and growth rate
title_full Delineation of proteome changes driven by cell size and growth rate
title_fullStr Delineation of proteome changes driven by cell size and growth rate
title_full_unstemmed Delineation of proteome changes driven by cell size and growth rate
title_short Delineation of proteome changes driven by cell size and growth rate
title_sort delineation of proteome changes driven by cell size and growth rate
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483106/
https://www.ncbi.nlm.nih.gov/pubmed/36133920
http://dx.doi.org/10.3389/fcell.2022.980721
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