Palladin是一種微絲關聯蛋白，研究顯示其參與了非肌肉組織的分化過程。而palladin在骨骼肌的功能至今尚未被研究透徹。目前的研究發現，palladin在不同時期的sacromere組裝過程中有不連續的分布。在肌肉纖維形成的過程中，palladin與微絲(actin)，α-actinin和MyHC有共區域化(colocalization)的情形，而在成熟的肌肉組織中，palladin則聚集於I-Z-I條帶。除此之外，研究發現palladin曾與集結蛋白短暫參與肌肉生成過程。因此我們進一步探討palladin缺失是否干擾微絲組裝過程進而對肌肉生成造成影響。

我們透過siRNA技術將C2C12小鼠肌原母細胞中的palladin knockdown，發現在palladin缺失的情況下，會減少細胞的遷移行為，而細胞活性和MyHC蛋白的表現量則會上升。為了釐清此現象，我們進一步用lentivirus-based的shRNA技術將palladin穩定knockdown。Palladin的缺失導致肌肉提前分化，伴隨著細胞凋亡的減少。而提前成熟的肌肉生成過程部分是受到p21,myogenin與MyHC的加速誘導所導致。因此，我們推測palladin在分化早期是扮演一個負調控的腳色。然而，palladin受到抑制的細胞所生成的肌小管比起控制組還細，並且細胞核的數目也較少。值得注意的是，另一個肌生成的負調控者─myostatin蛋白，在palladin缺失的肌小管中的表現量上升，可能在palladin缺失所導致的肌肉分化後期損傷扮演重要腳色。除此之外，140-kDa palladin的過度表現會抑制肌原母細胞的分化，而200-kDa and 90-kDa palladin的過度表現則會加速其分化速率。再者，palladin的抑制亦會減少integrin β3移動到細胞黏著點附近表現。總結來說，我們的研究結果揭示palladin是參與肌生成過程的重要腳色，並且不同的isoforms具有不同的功能。

Palladin is an actin-associated protein that has been shown to be involved in differentiation processes in non-muscle tissues. However, its function in skeletal muscle has rarely been studied. In the current study, palladin was found discretely organized in different stages of sarcomere assembly, colocalized with actin, α-actinin and and myosin heavy chain (MyHC) during myofibril formation but concentrated in I-Z-I bands of adult muscle. The observation suggested that palladin temporally engages with sarcomeric proteins during myogenesis. We next investigate whether myogenesis is influenced by the depletion of palladin expression known to interfere with the actin cytoskeleton dynamic required for myogenesis. siRNA-mediated knockdown of palladin in C2C12 myoblasts decreased cell migration but enhanced vitality and promoted MyHC expression. To clarify this observation, palladin was stably knocked-down using lentivirus-based shRNA strategy. Palladin deficiency leaded to precocious myogenic differentiation with a concomitant reduction in cell apoptosis. This premature myogenesis is caused, in part, by an accelerated induction of p21, myogenin and MyHC. Thus, these results suggest the negative regulator role of palladin in early differentiation phases. However, palladin-inhibited cells formed thinner myotubes with fewer myonuclei compared to those of the control. It is noteworthy that a negative regulator of myogenesis, myostatin, was activated in palladin-deficient myotubes, suggesting the palladin-mediated impairment of late-stage myogenesis. Additionally, overexpression of 140-kDa palladin inhibited myoblast differentiation while 200-kDa and 90-kDa palladin-overexpressed cells displayed an enhanced differentiation rate. Furthermore, the inhibition of palladin expression decreased the localization of integrin β3 into nascent adhesions. Collectively, our results highlight the involvement of palladin protein and the discrete functions of palladin isoforms in myogenesis in vitro.

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