Prelamin A accumulation attenuates Rac1 activity and increases the intrinsic migrational persistence of aged vascular smooth muscle cells

Lauren J. Porter; Mark R. Holt; Daniel Soong; Catherine M. Shanahan; Derek T. Warren

doi:10.3390/cells5040041

Prelamin A accumulation attenuates Rac1 activity and increases the intrinsic migrational persistence of aged vascular smooth muscle cells

Lauren J. Porter, Mark R. Holt, Daniel Soong, Catherine M. Shanahan, Derek T. Warren^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Article number	41
Journal	Cells
Volume	5
Issue number	4
DOIs	https://doi.org/10.3390/cells5040041
Publication status	Published - 15 Nov 2016

Keywords

Migratory persistence
Prelamin A
Rac1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Prelamin A accumulation attenuates Rac1 activity and increases the intrinsic migrational persistence of aged vascular smooth muscle cells",

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.",

keywords = "Migratory persistence, Prelamin A, Rac1",

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year = "2016",

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doi = "10.3390/cells5040041",

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T1 - Prelamin A accumulation attenuates Rac1 activity and increases the intrinsic migrational persistence of aged vascular smooth muscle cells

AU - Porter, Lauren J.

AU - Holt, Mark R.

AU - Soong, Daniel

AU - Shanahan, Catherine M.

AU - Warren, Derek T.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - 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.

AB - 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.

KW - Migratory persistence

KW - Prelamin A

KW - Rac1

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DO - 10.3390/cells5040041

M3 - Article

SN - 1016-8478

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JO - Cells

JF - Cells

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ER -

Prelamin A accumulation attenuates Rac1 activity and increases the intrinsic migrational persistence of aged vascular smooth muscle cells

Abstract

Keywords

UN SDGs

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