Kang J S, Mulieri P J, Miller C, Sassoon D A, Krauss R S
Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Cell Biol. 1998 Oct 19;143(2):403-13. doi: 10.1083/jcb.143.2.403.
CDO, a member of the Ig/fibronectin type III repeat subfamily of transmembrane proteins that includes the axon guidance receptor Robo, was identified by virtue of its down-regulation by the ras oncogene. We report here that one prominent site of cdo mRNA expression during murine embryogenesis is the early myogenic compartment (newly formed somites, dermomyotome and myotome). CDO is expressed in proliferating and differentiating C2C12 myoblasts and in myoblast lines derived by treating 10T1/2 fibroblasts with 5-azacytidine, but not in parental 10T1/2 cells. Overexpression of CDO in C2C12 cells accelerates differentiation, while expression of secreted soluble extracellular regions of CDO inhibits this process. Oncogenic Ras is known to block differentiation of C2C12 cells via downregulation of MyoD. Reexpression of CDO in C2C12/Ras cells induces MyoD; conversely, MyoD induces CDO. Reexpression of either CDO or MyoD rescues differentiation of C2C12/Ras cells without altering anchorage-independent growth or morphological transformation. CDO and MyoD are therefore involved in a positive feedback loop that is central to the inverse relationship between cell differentiation and transformation. It is proposed that CDO mediates, at least in part, the effects of cell-cell interactions between muscle precursors that are critical in myogenesis.
CDO是跨膜蛋白Ig/纤连蛋白III型重复亚家族的成员，该家族包括轴突导向受体Robo，它是通过ras癌基因对其下调而被鉴定出来的。我们在此报告，在小鼠胚胎发育过程中，cdo mRNA表达的一个主要部位是早期生肌区室（新形成的体节、皮肌节和肌节）。CDO在增殖和分化的C2C12成肌细胞以及用5-氮杂胞苷处理10T1/2成纤维细胞衍生的成肌细胞系中表达，但在亲本10T1/2细胞中不表达。CDO在C2C12细胞中的过表达加速了分化，而CDO分泌的可溶性细胞外区域的表达则抑制了这一过程。已知致癌性Ras通过下调MyoD来阻断C2C12细胞的分化。CDO在C2C12/Ras细胞中的重新表达诱导了MyoD；相反，MyoD诱导了CDO。CDO或MyoD的重新表达挽救了C2C12/Ras细胞的分化，而不改变非锚定依赖性生长或形态转化。因此，CDO和MyoD参与了一个正反馈回路，该回路对于细胞分化和转化之间的反比关系至关重要。有人提出，CDO至少部分介导了肌肉前体细胞之间细胞间相互作用的影响，这在肌生成中至关重要。
