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Cardiovasc Res. 2013 Dec 1;100(3):461-71. doi: 10.1093/cvr/cvt207. Epub 2013 Aug 23.

Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration.

Author information

1
Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.

Abstract

AIMS:

Cysteine-rich protein (CRP) 2, a member of the LIM-only CRP family that contains two LIM domains, is expressed in vascular smooth muscle cells (VSMCs) of blood vessels and functions to repress VSMC migration and vascular remodelling. The goal of this study was to define the molecular mechanisms by which CRP2 regulates VSMC migration.

METHODS AND RESULTS:

Transfection of VSMCs with CRP2-EGFP constructs revealed that CRP2 associated with the actin cytoskeleton. In response to chemoattractant stimulation, Csrp2 (mouse CRP2 gene symbol)-deficient (Csrp2(-/-)) VSMCs exhibited increased lamellipodia formation. Re-introduction of CRP2 abrogated the enhanced lamellipodia formation and migration of Csrp2(-/-) VSMCs following chemoattractant stimulation. Mammalian 2-hybrid and co-immunoprecipitation assays demonstrated that CRP2 interacts with p130Cas, a scaffold protein important for lamellipodia formation and cell motility. Immunofluorescence staining showed that CRP2 colocalized with phospho-p130Cas at focal adhesions (FAs)/terminal ends of stress fibres in non-migrating cells. Interestingly, in migrating cells phospho-p130Cas localized to the leading edge of lamellipodia and FAs, whereas CRP2 was restricted to FAs and stress fibres. Furthermore, we demonstrated that p130Cas expression and phosphorylation promote neointima formation following arterial injury.

CONCLUSION:

These studies demonstrate that CRP2 sequesters p130Cas at FAs, thereby reducing lamellipodia formation and blunting VSMC migration.

KEYWORDS:

Cysteine-rich protein 2; Migration; P130Cas; Vascular smooth muscle cells

PMID:
23975851
PMCID:
PMC3826702
DOI:
10.1093/cvr/cvt207
[Indexed for MEDLINE]
Free PMC Article
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