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Application of Statistical Models to Study Protein Stability in Subcellular Compartments

  • Author(s): Xiao, Shaohua
  • Advisor(s): Xu, Hongquan
  • et al.
Abstract

Gap junction protein connexin-43 (Cx43) is essential for intercellular communication and synchronous muscle contraction of the mammalian heart. Cx43 is enriched in the intercalated discs in normal hearts, but redistributed in arrhythmic failing hearts. To understand the pathophysiological mechanisms for arrhythmias and guide therapeutic interventions, it will be important to assess whether the mis-localized Cx43 remains stable or undergoes rapid turnover. The M213L mutation in Cx43 has been shown to impair delivery of the protein to the intercalated discs. Stabilities of the wild type and M213L mutated Cx43 protein in subcellular fractions have been reported. Here we applied multiple statistical models to the protein stability data to further analyze the effects of subcellular compartments and mutation on protein degradation. Our results indicated that fraction, but not the M213L mutation, affected Cx43 degradation, with the protein in the non-junctional fraction being degraded rapidly.

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