The fitness cost and benefit of phase-separated protein deposits
Sánchez de Groot, Natalia (Centre de Regulació Genòmica)
Torrent, Marc (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ravarani, Charles N. J. (Medical Research Council Laboratory of Molecular Biology)
Trusina, Ala (Niels Bohr Institute)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Babu, Madam M. (Medical Research Council Laboratory of Molecular Biology)

Date:	2019
Abstract:	Phase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane-less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase-separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can influence cell-to-cell variation in free protein abundance between individuals of a cell population (i. e. , gene expression noise). This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase-separated assemblies and may influence cell fitness.
Grants:	European Commission 330352 European Commission 299105 Agencia Estatal de Investigación SAF2017-82158-R Ministerio de Economía y Competitividad SAF2015-72518-EXP Ministerio de Economía y Competitividad RYC-2012-09999
Note:	Altres ajuts: Beatriu de Pinos fellowships
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cell fitness ; Natural selection ; Phase separation ; Phenotypic diversity ; Protein deposit
Published in:	Molecular systems biology, Vol. 15, issue 4 (April 2019) , art. e8075, ISSN 1744-4292

DOI: 10.15252/msb.20178075
PMID: 30962358

20 p, 3.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles