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

Abstract

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.