Mechanism of PDX-1 protein transduction

Hirofumi Noguchi, Masayuki Matsushita, Shinichi Matsumoto, Yun Fei Lu, Hideki Matsui, Susan Bonner-Weir

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Abstract

PDX-1 plays a central role in differentiation of insulin-producing cells. We previously reported that exogenous PDX-1 protein can permeate cells and induce insulin gene expression in progenitor cells. These data suggest a strategy for facilitating differentiation into insulin-producing cells. Here we show the mechanism of PDX-1 protein transduction. Initially, a punctate cytoplasmic distribution of PDX-1 protein transduction domain (PTD), which co-localized with an endosomal marker, was observed in treated cells. However, homogeneous distribution of PDX-1-PTD was observed in some cells, indicating that PDX-1 is transduced by endocytosis and then released. The experiments using inhibitors suggested that the PDX-1 is transported through the Golgi complex and to the endoplasmic reticulum. Moreover, we observed in real-time PDX-1-PTD release from endosomes. These data suggest that mechanism of transduction of PDX-1 protein is by endocytosis and subsequent release from the endosome homogeneously in cytoplasm and nuclei, and that PDX-1 protein transduction could be a valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number1
DOIs
Publication statusPublished - Jun 24 2005

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Keywords

  • Endocytosis
  • Endosomal release
  • Islet transplantation
  • PDX-1
  • Protein transduction domain
  • Regeneration

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Noguchi, H., Matsushita, M., Matsumoto, S., Lu, Y. F., Matsui, H., & Bonner-Weir, S. (2005). Mechanism of PDX-1 protein transduction. Biochemical and Biophysical Research Communications, 332(1), 68-74. https://doi.org/10.1016/j.bbrc.2005.04.092