Characterization of palladin function roles in skeletal muscle differentiation

  • 阮 玉鴛兒

Student thesis: Doctoral Thesis


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 ?-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
Date of Award2015 Jun 25
Original languageEnglish
SupervisorHao-Ven Wang (Supervisor)

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