The basic route of nuclear‐targeted transport of IGF‐1/IGF‐1R and potential biological functions in intestinal epithelial cells

OBJECTIVES: Insulin‐like growth factor (IGF‐1) plays an important role in many biological processes in the intestinal tract. However, the cellular behaviour and characteristics of IGF‐1/IGF‐1R in intestinal cells remain unclear. MATERIALS AND METHODS: A series of techniques (such as indirect immunofluorescence, co‐localization and Western blot) have been used to systematically study the cellular behaviour of IGF‐1/IGF‐1R on intestinal cells. RESULTS: We found that IGF‐1 can not only internalize into the cytoplasm, but also transport into the cell nuclei. We systematically studied the detailed molecular pathways of IGF‐1/IGF‐1R’s nuclear translocation. We found that IGF‐1R underwent clathrin‐mediated endocytosis into cells and then entered into Rab‐5‐positive endosomes. Dynein/dynactin were used as motors to drive Rab‐5‐positive endosomes carrying IGF‐1R (cargo molecule) to Golgi apparatus (transit station) along the surface of the microtubule. IGF‐1 and/or IGF‐1R entered the cell nuclei through NPC (nuclear pore complex), a process mediated by NUP358. Further study indicated that nuclear localization of IGF‐1 and/or IGF‐1R promoted cell proliferation and increased the nuclear residence time of signalling molecules activated by IGF‐1. Further experiments showed that IGF‐1R may regulate the transcription of genes in the cell nuclei, indicating that nuclear‐localized IGF‐1R plays an important in cell proliferation. CONCLUSIONS: In short, we revealed the molecular mechanism by which IGF‐1/IGF‐1R transports into the cell nuclei of intestinal cells. More importantly, the current work showed that the nuclear‐localized IGF‐1R has important biological functions.