Low Robert, Léguillette Renaud, Lauzon Anne-Marie
University of Vermont, Burlington, VT 05405, United States.
Int J Biochem Cell Biol. 2006;38(11):1862-74. doi: 10.1016/j.biocel.2006.03.014. Epub 2006 Apr 6.
In smooth muscle, alternative mRNA splicing of a single gene produces four myosin heavy chain (SMMHC) isoforms. Two of these isoforms differ by the presence [(+)insert] or absence [(-)insert] of a seven amino acid insert in the motor domain. This insert enhances the kinetic properties of myosin at the molecular level but its exact role at the cell and tissue levels still has to be elucidated. This review focuses on the expression and biological functions of the (+)insert isoform. Current knowledge is summarized regarding its tissue distribution in animals and humans. Studies at the molecular, cellular and tissue levels that aimed at understanding the contribution of this isoform to smooth muscle mechanical function are presented with a particular focus on velocity of shortening. In addition, the altered expression of the (+)insert isoform in diseases and models of diseases and the compensatory mechanisms that occur when the (+)insert is knocked out are discussed. The need for additional studies on the relationship of this isoform to contractile performance and how expression of this isoform is regulated are also considered.
在平滑肌中,单个基因的可变mRNA剪接产生四种肌球蛋白重链(SMMHC)同工型。其中两种同工型的区别在于运动结构域中是否存在一个七氨基酸插入片段[(+)插入]或不存在[(-)插入]。该插入片段在分子水平上增强了肌球蛋白的动力学特性,但其在细胞和组织水平的确切作用仍有待阐明。本综述聚焦于(+)插入同工型的表达及生物学功能。总结了关于其在动物和人类组织分布的现有知识。介绍了旨在了解该同工型对平滑肌机械功能贡献的分子、细胞和组织水平研究,特别关注缩短速度。此外,还讨论了(+)插入同工型在疾病和疾病模型中的表达改变以及当(+)插入被敲除时发生的补偿机制也进行了讨论。还考虑了对该同工型与收缩性能关系进行更多研究的必要性以及该同工型的表达是如何调控的。