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Quantitative proteomics reveals altered expression of actin binding proteins after LMNA knockdown in human dermal fibroblasts

Tobias Corne (UGent) , Tom Sieprath (UGent) , Jonathan Vandenbussche (UGent) , Kris Gevaert (UGent) and Winnok De Vos (UGent)
Author
Organization
Abstract
The nuclear lamina physically supports the cell nucleus and has a central role in gene regulation. Mutations in the LMNA gene, which encodes A-type lamins, cause a wide spectrum of tissue-specific and systemic diseases collectively called laminopathies. To elucidate the molecular mechanisms underlying this phenotypic diversity, we set out to identify changes in the proteome upon specific lamin perturbations. More specifically, mature lamin A was reduced by sustained knockdown of LMNA in human dermal fibroblasts. To quantitatively compare protein composition, we made use of SILAC-based shotgun proteomics. The expression of 48 proteins was altered after LMNA knockdown. Gene Ontology analysis of the most significant hits revealed that the largest fraction of the differentially produced proteins in lamin A/C depleted cells were cytoskeletal proteins, more specifically those involved in actin cytoskeleton organization, such as ACTR2 and ACTR3 which are components of the ARP2/3 complex and FSCN1 which plays a critical role in cell migration, motility, adhesion and cellular interactions. Indeed, impaired wound healing and focal adhesion was observed in lamin A/C depleted fibroblasts. Furthermore, decreased expression of FSCN1 was correlated with a downregulation of IL6 and STAT3, which might be the instigators of the altered FSCN1 expression.
Keywords
SILAC, Quantitative proteomics, Cytoskeleton, LMNA, Nuclear lamina

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Chicago
Corne, Tobias, Tom Sieprath, Jonathan Vandenbussche, Kris Gevaert, and Winnok De Vos. 2015. “Quantitative Proteomics Reveals Altered Expression of Actin Binding Proteins After LMNA Knockdown in Human Dermal Fibroblasts.” In Nuclear Structure and Dynamics, EMBO Conference, Abstracts. EMBO.
APA
Corne, T., Sieprath, T., Vandenbussche, J., Gevaert, K., & De Vos, W. (2015). Quantitative proteomics reveals altered expression of actin binding proteins after LMNA knockdown in human dermal fibroblasts. Nuclear Structure and Dynamics, EMBO conference, Abstracts. Presented at the EMBO conference on Nuclear Structure and Dynamics, EMBO.
Vancouver
1.
Corne T, Sieprath T, Vandenbussche J, Gevaert K, De Vos W. Quantitative proteomics reveals altered expression of actin binding proteins after LMNA knockdown in human dermal fibroblasts. Nuclear Structure and Dynamics, EMBO conference, Abstracts. EMBO; 2015.
MLA
Corne, Tobias, Tom Sieprath, Jonathan Vandenbussche, et al. “Quantitative Proteomics Reveals Altered Expression of Actin Binding Proteins After LMNA Knockdown in Human Dermal Fibroblasts.” Nuclear Structure and Dynamics, EMBO Conference, Abstracts. EMBO, 2015. Print.
@inproceedings{7088071,
  abstract     = {The nuclear lamina physically supports the cell nucleus and has a central role in gene regulation. Mutations in the LMNA gene, which encodes A-type lamins, cause a wide spectrum of tissue-specific and systemic diseases collectively called laminopathies. To elucidate the molecular mechanisms underlying this phenotypic diversity, we set out to identify changes in the proteome upon specific lamin perturbations. More specifically, mature lamin A was reduced by sustained knockdown of LMNA in human dermal fibroblasts. To quantitatively compare protein composition, we made use of SILAC-based shotgun proteomics. The expression of 48 proteins was altered after LMNA knockdown. Gene Ontology analysis of the most significant hits revealed that the largest fraction of the differentially produced proteins in lamin A/C depleted cells were cytoskeletal proteins, more specifically those involved in actin cytoskeleton organization, such as ACTR2 and ACTR3 which are components of the ARP2/3 complex and FSCN1 which plays a critical role in cell migration, motility, adhesion and cellular interactions. Indeed, impaired wound healing and focal adhesion was observed in lamin A/C depleted fibroblasts. Furthermore, decreased expression of FSCN1 was correlated with a downregulation of IL6 and STAT3, which might be the instigators of the altered FSCN1 expression.},
  author       = {Corne, Tobias and Sieprath, Tom and Vandenbussche, Jonathan and Gevaert, Kris and De Vos, Winnok},
  booktitle    = {Nuclear Structure and Dynamics, EMBO conference, Abstracts},
  keyword      = {SILAC,Quantitative proteomics,Cytoskeleton,LMNA,Nuclear lamina},
  language     = {eng},
  location     = {Isle sur Sorgue, France},
  publisher    = {EMBO},
  title        = {Quantitative proteomics reveals altered expression of actin binding proteins after LMNA knockdown in human dermal fibroblasts},
  year         = {2015},
}