Smooth muscle cells on the move: the battle for actin.

Abstract

See article by Blindt et al. [2] (pages 630–639) in this issue. Restenosis has been troubling patients and cardiologists, following percutaneous transluminal coronary angioplasty (PTCA), since the technique was introduced [1]. Dedifferentiation, migration and proliferation of smooth muscle cell (SMC) can cause a new obstructive lesion, at the site of the mechanical intravascular balloon intervention. Gradually our knowledge about SMC mobility is increasing. This mobility is the consequence of SMC (de)differentiation. The ability of these cells to switch from a contractile to a synthetic/proliferative phenotype has been a prime target of research in the cardiovascular field. Although the different phenotypes of SMC have been known for years, the underlying signalling, changes in gene expression and protein activation and the mechanism of cell mobility adaptation, still remain to be resolved. Also the keys to the maintenance of SMC (de)differentiation are currently unknown. Many clues indicate a crucial role for actin stabilisation and assembly regulating proteins. In this issue important work is reported on the role of moesin, one of the actin binding proteins on SMC mobility by Blindt et al. [2]. The moesin gene is positioned on the X-chromosome and part of a protein family indicated by ERM (ezrin, radixin and moesin). All three proteins are composed of a N-terminal FERM domain (F: four point one protein), a central α-domain and a C-terminal tail domain. Inactivated moesin is folded such that the FERM domain bites and holds the tail. Upon phosphorylation of moesin the protein unfolds, whereafter the FERM domain binds to specific sites in the membrane (like for instance CD44, CD43, ICAM-1, ICAM-2 and l-selectin in lymphocytes), while the tail interacts with F-actin [3,4]. The activated protein therefore connects F-actin to the plasma membrane. Blindt et al. [2] showed the increased expression of moesin following PTCA … * Corresponding author. Tel.: +31-43-387-5095; fax: +31-43-387-7081 p.doevendans{at}cardio.azm.nl