School of Exercise and Rehabilitation Sciences, University of Toledo, Toledo, Ohio, USA.
Department of Biological Sciences, University of Toledo, Toledo, Ohio, USA.
Sci Rep. 2017 Jul 11;7(1):5094. doi: 10.1038/s41598-017-05283-3.
The overall objective of the study was to identify mechanisms through which intercellular adhesion molecule-1 (ICAM-1) augments the adhesive and fusogenic properties of myogenic cells. Hypotheses were tested using cultured myoblasts and fibroblasts, which do not constitutively express ICAM-1, and myoblasts and fibroblasts forced to express full length ICAM-1 or a truncated form lacking the cytoplasmic domain of ICAM-1. ICAM-1 mediated myoblast adhesion and fusion were quantified using novel assays and cell mixing experiments. We report that ICAM-1 augments myoblast adhesion to myoblasts and myotubes through homophilic trans-interactions. Such adhesive interactions enhanced levels of active Rac in adherent and fusing myoblasts, as well as triggered lamellipodia, spreading, and fusion of myoblasts through the signaling function of the cytoplasmic domain of ICAM-1. Rac inhibition negated ICAM-1 mediated lamellipodia, spreading, and fusion of myoblasts. The fusogenic property of ICAM-1-ICAM-1 interactions was restricted to myogenic cells, as forced expression of ICAM-1 by fibroblasts did not augment their fusion to ICAM-1+ myoblasts/myotubes. We conclude that ICAM-1 augments myoblast adhesion and fusion through its ability to self-associate and initiate Rac-mediated remodeling of the actin cytoskeleton.
本研究的总体目标是确定细胞间黏附分子-1（ICAM-1）增强成肌细胞黏附和融合特性的机制。使用培养的成肌细胞和成纤维细胞（不组成表达 ICAM-1），以及强制表达全长 ICAM-1 或缺乏 ICAM-1 细胞质域的截断形式的成肌细胞和成纤维细胞来检验假说。使用新的测定法和细胞混合实验来定量 ICAM-1 介导的成肌细胞黏附和融合。我们报告 ICAM-1 通过同源相互作用增强成肌细胞与成肌细胞和肌管的黏附。这种黏附相互作用增强了黏附和成融合的成肌细胞中活性 Rac 的水平，并通过 ICAM-1 细胞质域的信号功能触发了成肌细胞的片状伪足、扩展和融合。Rac 抑制消除了 ICAM-1 介导的成肌细胞的片状伪足、扩展和融合。ICAM-1-ICAM-1 相互作用的融合特性仅限于成肌细胞，因为成纤维细胞强制表达的 ICAM-1 并不能增强它们与 ICAM-1+成肌细胞/肌管的融合。我们得出结论，ICAM-1 通过其自我缔合和启动 Rac 介导的肌动蛋白细胞骨架重塑的能力来增强成肌细胞的黏附和融合。
