TY - JOUR
T1 - Mechanism of PDX-1 protein transduction
AU - Noguchi, Hirofumi
AU - Matsushita, Masayuki
AU - Matsumoto, Shinichi
AU - Lu, Yun Fei
AU - Matsui, Hideki
AU - Bonner-Weir, Susan
N1 - Funding Information:
This research was supported by NIH Grants DK 61251, DK 44523, the Joslin DERC media core (DK36836), the Diabetes Research and Wellness Foundation and an important group of private donors, and by Grant-in-Aid for Scientific Research on Priority Areas (C) “Medical Genome Science” from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2005/6/24
Y1 - 2005/6/24
N2 - 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.
AB - 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.
KW - Endocytosis
KW - Endosomal release
KW - Islet transplantation
KW - PDX-1
KW - Protein transduction domain
KW - Regeneration
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U2 - 10.1016/j.bbrc.2005.04.092
DO - 10.1016/j.bbrc.2005.04.092
M3 - Article
C2 - 15896300
AN - SCOPUS:19344365201
VL - 332
SP - 68
EP - 74
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -