PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes
PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes
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DOI：
10.1242/jcs.03290
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发表时间：
2006-12-15
影响因子：
4
通讯作者：
Inui, Makoto
中科院分区：
文献类型：
--
作者：
Ko, Ji-Ae;Kimura, Yoshihiro;Inui, Makoto
PDZRN 3在其N-末端区域含有环指基序，在其中心区域含有两个PDZ结构域，并且在其C-末端含有PDZ结构域的共有结合基序。它在计算机上被鉴定为称为LNX 1或SEMCAP 1的蛋白质的同源物，其具有泛素连接酶活性并结合膜蛋白脑信号蛋白4C。然而，PDZRN 3本身以前没有被表征。我们现在已经评估了PDZRN 3的性质和功能。PDZRN 3基因在包括心脏、骨骼肌和肝脏在内的多种人体组织中表达，并且其在小鼠骨骼肌中的表达受到发育调节。无论是C2 C12小鼠骨骼肌成肌细胞分化成肌管和损伤诱导的肌肉再生在体内被发现伴随着PDZRN 3的上调。在C2 C12细胞中，PDZRN 3表达的分化相关增加在肌生成素表达的增加之后并且在肌球蛋白重链表达的增加之前。通过RNA干扰去除PDZRN 3抑制C2 C12细胞中肌管的形成以及相关的肌球蛋白重链的上调。我们的数据表明，PDZRN 3在成肌细胞分化成肌管中起着重要的作用，其作用是在成肌蛋白的下游或独立于成肌蛋白。
PDZRN3 contains a RING-finger motif in its N-terminal region, two PDZ domains in its central region and a consensus-binding motif for PDZ domains at its C-terminus. It was identified in silico as a homolog of the protein known as LNX1 or SEMCAP1, which possesses ubiquitin ligase activity and binds the membrane protein Semaphorin 4C. However, PDZRN3 itself has not previously been characterized. We have now evaluated the properties and functions of PDZRN3. The PDZRN3 gene was shown to be expressed in various human tissues including the heart, skeletal muscle and liver and its expression in mouse skeletal muscle was developmentally regulated. Both the differentiation of C2C12 mouse skeletal myoblasts into myotubes and injury-induced muscle regeneration in vivo were found to be accompanied by up-regulation of PDZRN3. The differentiation-associated increase in the expression of PDZRN3 in C2C12 cells follows that of myogenin and precedes that of myosin heavy chain. Depletion of PDZRN3 by RNA interference inhibited the formation of myotubes as well as the associated up-regulation of myosin heavy chain in C2C12 cells. Our data suggest that PDZRN3 plays an essential role in the differentiation of myoblasts into myotubes by acting either downstream or independently of myogenin.