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Cells 2016, 5(4), 41; doi:10.3390/cells5040041

Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells

1
British Heart Foundation Centre of Research Excellence, Cardiovascular Division, King’s College London, London SE5 9NU, UK
2
Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London SE1 1UL, UK
3
MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK
4
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Thomas Dechat
Received: 15 September 2016 / Revised: 10 November 2016 / Accepted: 11 November 2016 / Published: 15 November 2016
(This article belongs to the Collection Lamins and Laminopathies)
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Abstract

Vascular smooth muscle cell (VSMC) motility is essential during both physiological and pathological vessel remodeling. Although ageing has emerged as a major risk factor in the development of cardiovascular disease, our understanding of the impact of ageing on VSMC motility remains limited. Prelamin A accumulation is known to drive VSMC ageing and we show that presenescent VSMCs, that have accumulated prelamin A, display increased focal adhesion dynamics, augmented migrational velocity/persistence and attenuated Rac1 activity. Importantly, prelamin A accumulation in proliferative VSMCs, induced by depletion of the prelamin A processing enzyme FACE1, recapitulated the focal adhesion, migrational persistence and Rac1 phenotypes observed in presenescent VSMCs. Moreover, lamin A/C-depleted VSMCs also display reduced Rac1 activity, suggesting that prelamin A influences Rac1 activity by interfering with lamin A/C function at the nuclear envelope. Taken together, these data demonstrate that lamin A/C maintains Rac1 activity in VSMCs and prelamin A disrupts lamin A/C function to reduce Rac1 activity and induce migrational persistence during VSMC ageing. View Full-Text
Keywords: prelamin A; migratory persistence; Rac1 prelamin A; migratory persistence; Rac1
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MDPI and ACS Style

Porter, L.J.; Holt, M.R.; Soong, D.; Shanahan, C.M.; Warren, D.T. Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells. Cells 2016, 5, 41.

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