دانلود رایگان مقاله پروستاگلاندین E2 تسهیل جایگزینی درون سلولی گیرنده EP4

Abstract

abstract Prostaglandin E2 (PGE2) is a lipid mediator released from the phospholipid membranes that mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4). There is growing evidence for the important role of the PGE2/EP4 signaling in the nervous system. Previous studies in our lab show that the expression of the EP4 receptor is significantly higher during the neurogenesis period in the mouse. We also showed that in mouse neuroblastoma cells, the PGE2/EP4 receptor signaling pathway plays a role in regulation of intracellular calcium via a phosphoinositide 3-kinase (PI3K)-dependent mechanism. Recent research indicates that the functional importance of the EP4 receptor depends on its subcellular localization. PGE2-induced EP4 externalization to the plasma membrane of primary sensory neurons has been shown to play a role in the pain pathway. In the present study, we detected a novel PGE2–dependent subcellular trafficking of the EP4 receptor in neuroectodermal (NE-4C) stem cells and differentiated NE-4C neuronal cells. We show that PGE2 induces EP4 externalization from the Golgi apparatus to the plasma membrane in NE-4C stem cells. We also show that the EP4 receptors translocate to growth cones of differentiating NE-4C neuronal cells and that a higher level of PGE2 enhances its growth cone localization. These results demonstrate that the EP4 receptor relocation to the plasma membrane and growth cones in NE-4C cells is PGE2 dependent. Thus, the functional role of the PGE2/EP4 pathway in the developing nervous system may depend on the subcellular localization of the EP4 receptor.

4. Discussion

The results of this study show that 10 mM PGE2 induces EP4 externalization from its previously characterized localization in the Golgi apparatus [23] to the plasma membrane in undifferentiated NE-4C stem cells. 1 mM PGE2 did not have a significant effect on undifferentiated NE-4C stem cells, indicating that EP4-translocation may be PGE2 concentration-dependent. Interestingly, we also found that in differentiated NE-4C neuronal cells, 1 or 10 mM PGE2 enhanced EP4 trafficking to the growth cones. The observed subcellular translocation of the EP4 receptor from its normal location in the Golgi apparatus to the plasma membrane and growth cones indicates that it may play an important role in early function of neuronal cells.