Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle
Date
2024-01
Authors
Kajuluri, Lova Prasadareddy
Lyu, Qing Rex
Doja, Jaser
Kumar, Ajay
Wilson, Michael P.
Sgrizzi, Samantha R.
Rezaeimanesh, Elika
Miano, Joseph M.
Morgan, Kathleen G.
Version
Published version
OA Version
Citation
L.P. Kajuluri, Q.R. Lyu, J. Doja, A. Kumar, M.P. Wilson, S.R. Sgrizzi, E. Rezaeimanesh, J.M. Miano, K.G. Morgan. 2024. "Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle." Journal of Cellular and Molecular Medicine, Volume 28, Issue 1, pp.e18025-. https://doi.org/10.1111/jcmm.18025
Abstract
Smooth muscle cell (SMC) contraction and vascular tone are modulated by phosphorylation and multiple modifications of the thick filament, and thin filament regulation of SMC contraction has been reported to involve extracellular regulated kinase (ERK). Previous studies in ferrets suggest that the actin-binding protein, calponin 1 (CNN1), acts as a scaffold linking protein kinase C (PKC), Raf, MEK and ERK, promoting PKC-dependent ERK activation. To gain further insight into this function of CNN1 in ERK activation and the regulation of SMC contractility in mice, we generated a novel Calponin 1 knockout mouse (Cnn1 KO) by a single base substitution in an intronic CArG box that preferentially abolishes expression of CNN1 in vascular SMCs. Using this new Cnn1 KO mouse, we show that ablation of CNN1 has two effects, depending on the cytosolic free calcium level: (1) in the presence of elevated intracellular calcium caused by agonist stimulation, Cnn1 KO mice display a reduced amplitude of stress and stiffness but an increase in agonist-induced ERK activation; and (2) during intracellular calcium depletion, in the presence of an agonist, Cnn1 KO mice exhibit increased duration of SM tone maintenance. Together, these results suggest that CNN1 plays an important and complex modulatory role in SMC contractile tone amplitude and maintenance.
Description
License
© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.