Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom.
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19927-32. doi: 10.1073/pnas.1007381107. Epub 2010 Nov 1.
Calcium signaling is essential for the differentiation of many cell types, including skeletal muscle cells, but its mechanisms remain elusive. Here we demonstrate a crucial role for nicotinic acid adenine dinucleotide phosphate (NAADP) signaling in skeletal muscle differentiation. Although the inositol trisphosphate pathway may have a partial role to play in this process, the ryanodine signaling cascade is not involved. In both skeletal muscle precursors and C2C12, cells interfering with NAADP signaling prevented differentiation, whereas promoting NAADP signaling potentiated differentiation. Moreover, siRNA knockdown of two-pore channels, the target of NAADP, attenuated differentiation. The data presented here strongly suggest that in myoblasts, NAADP acts at acidic organelles on the recently discovered two-pore channels to promote differentiation.
钙信号对于许多细胞类型的分化是必不可少的，包括骨骼肌细胞，但其机制仍难以捉摸。在这里，我们证明了烟酰胺腺嘌呤二核苷酸磷酸（NAADP）信号在骨骼肌分化中的关键作用。尽管三磷酸肌醇途径在这个过程中可能起到一定的作用，但ryanodine 信号级联反应不参与其中。在骨骼肌前体细胞和 C2C12 细胞中，干扰 NAADP 信号的细胞阻止了分化，而促进 NAADP 信号则增强了分化。此外，用 siRNA 敲低 NAADP 的靶点——双孔通道，也减弱了分化。这里呈现的数据强烈表明，在成肌细胞中，NAADP 作用于最近发现的双孔通道上的酸性细胞器，以促进分化。
