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Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity

Davina Tondeleir UGent, Anja Lambrechts UGent, Matthias Müller, Veronique Jonckheere UGent, Thierry Doll, Drieke Vandamme UGent, Karima Bakkali UGent, Davy Waterschoot UGent, Marianne Lemaistre and Olivier Debeir, et al. (2012) MOLECULAR & CELLULAR PROTEOMICS. 11(8). p.255-271
abstract
Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic beta- and gamma-actin. Because of the presence and localized translation of beta-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates beta-actin in gene regulation. Cell migration without beta-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking beta-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, beta-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of beta-actin knockout cells. This also explains why reintroducing beta-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in beta- actin knockout cells based on increased Rho-ROCK signaling and increased TGF beta production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of beta- actin knockout cells indicating that other actins compensate for beta- actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but beta-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation.
Please use this url to cite or link to this publication:
author
organization
alternative title
Cells lacking beta-actin are genetically reprogrammed and maintain conditional migratory capacity
year
type
journalArticle (original)
publication status
published
subject
keyword
EXPRESSION, PROTEINS, HNRNP-U, RHO-GTPASES, AMINO-ACIDS, INTRACELLULAR-LOCALIZATION, NUCLEAR ACTIN, MESSENGER-RNA, VASCULAR SMOOTH-MUSCLE, RNA-POLYMERASE-II
journal title
MOLECULAR & CELLULAR PROTEOMICS
Mol. Cell. Proteomics
volume
11
issue
8
pages
255 - 271
Web of Science type
Article
Web of Science id
000308024200004
JCR category
BIOCHEMICAL RESEARCH METHODS
JCR impact factor
7.251 (2012)
JCR rank
5/74 (2012)
JCR quartile
1 (2012)
ISSN
1535-9476
DOI
10.1074/mcp.M111.015099
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3031195
handle
http://hdl.handle.net/1854/LU-3031195
date created
2012-10-18 13:45:07
date last changed
2012-10-18 14:33:44
@article{3031195,
  abstract     = {Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic beta- and gamma-actin. Because of the presence and localized translation of beta-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates beta-actin in gene regulation. Cell migration without beta-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking beta-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, beta-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of beta-actin knockout cells. This also explains why reintroducing beta-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in beta- actin knockout cells based on increased Rho-ROCK signaling and increased TGF beta production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of beta- actin knockout cells indicating that other actins compensate for beta- actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but beta-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation.},
  author       = {Tondeleir, Davina and Lambrechts, Anja and M{\"u}ller, Matthias and Jonckheere, Veronique and Doll, Thierry and Vandamme, Drieke and Bakkali, Karima and Waterschoot, Davy and Lemaistre, Marianne and Debeir, Olivier and Decaestecker, Christine and Hinz, Boris and Staes, An and Timmerman, Evy and Colaert, Niklaas and Gevaert, Kris and Vandekerckhove, Jo{\"e}l and Ampe, Christophe},
  issn         = {1535-9476},
  journal      = {MOLECULAR \& CELLULAR PROTEOMICS},
  keyword      = {EXPRESSION,PROTEINS,HNRNP-U,RHO-GTPASES,AMINO-ACIDS,INTRACELLULAR-LOCALIZATION,NUCLEAR ACTIN,MESSENGER-RNA,VASCULAR SMOOTH-MUSCLE,RNA-POLYMERASE-II},
  language     = {eng},
  number       = {8},
  pages        = {255--271},
  title        = {Cells lacking \ensuremath{\beta}-actin are genetically reprogrammed and maintain conditional migratory capacity},
  url          = {http://dx.doi.org/10.1074/mcp.M111.015099},
  volume       = {11},
  year         = {2012},
}

Chicago
Tondeleir, Davina, Anja Lambrechts, Matthias Müller, Veronique Jonckheere, Thierry Doll, Drieke Vandamme, Karima Bakkali, et al. 2012. “Cells Lacking Β-actin Are Genetically Reprogrammed and Maintain Conditional Migratory Capacity.” Molecular & Cellular Proteomics 11 (8): 255–271.
APA
Tondeleir, D., Lambrechts, A., Müller, M., Jonckheere, V., Doll, T., Vandamme, D., Bakkali, K., et al. (2012). Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity. MOLECULAR & CELLULAR PROTEOMICS, 11(8), 255–271.
Vancouver
1.
Tondeleir D, Lambrechts A, Müller M, Jonckheere V, Doll T, Vandamme D, et al. Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity. MOLECULAR & CELLULAR PROTEOMICS. 2012;11(8):255–71.
MLA
Tondeleir, Davina, Anja Lambrechts, Matthias Müller, et al. “Cells Lacking Β-actin Are Genetically Reprogrammed and Maintain Conditional Migratory Capacity.” MOLECULAR & CELLULAR PROTEOMICS 11.8 (2012): 255–271. Print.