Study of EBP50 and ERM proteins in vascular smooth muscle
(2011)
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Details
- Authors
- Supervisors
- Morel, Nicole
- Abstract
- (en) The contractile tone of smooth muscle cells (VSMC) in the vascular wall controls the blood flow by modulating the arterial diameter. In pathological conditions, these cells switch from a contractile phenotype towards a more synthetic, migratory phenotype, leading to vascular diseases such as atherosclerosis or hyperplasia. Rho kinase (ROCK) plays a major role in the regulation of the contractile properties of myofilaments but also in calcium entry or the regulation of actin polymerization. The aim of the present study was to investigate the role of ERM proteins, known to be substrates of ROCK and their binding partner, EBP50, in the modulation of VSMC contraction or migration. We have identified ROCK and PKC as protein kinases involved in the phosphorylation and activation of ERM proteins in intact arteries. Among ERM proteins, moesin was found to interact with EBP50 in a ROCK-dependent manner, following noradrenaline stimulation. In addition to moesin, EBP50 was also found to interact with several cytoskeleton-related proteins. Both moesin and EBP50 depletion in mesenteric artery increased noradrenaline-evoked contraction, in a calcium-independent manner, suggesting that the interaction between moesin and EBP50 leads to the inhibition of artery contraction. Further work in cultured cells highlighted the role of EBP50 in VSMC migration. EBP50 depletion induced the disassembly of myosin IIa fibers, the polymerization of microtubule network, the activation of Rac1, the formation of lamellipodia and trailing tails and thus the migration of the cell. These results suggest that EBP50 may exert a protective role against VSMC migration. In conclusion, our work shed light on the involvement of ERM proteins and EBP50 in the modulation of VSMC cytoskeleton, contributing to the regulation of cell contraction or migration. The present results indicate that these proteins could play a protective role in the switch from a contractile phenotype towards a synthetic, migratory phenotype.
- Affiliations
Citations
Baeyens, N. (2011). Study of EBP50 and ERM proteins in vascular smooth muscle. https://hdl.handle.net/2078.5/151151