MAPKシグナルを空間的に制御するプラットフォームとしてのRNA顆粒の役割

• Published in: 日本薬理学会年会要旨集 p. 1-SS-14
• Main Authors: 土屋, 葵子, 神田, 勇輝, 永井, 善紀, 田中, 妙美, 水野, 綾美, 冨本, 尚史, 杉浦, 麗子
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2019
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.92.0_1-SS-14

Protein kinase C (PKC) family plays crucial roles in a wide variety of cellular functions and dysregulation of PKC signaling leads to pathophysiological states including cancer and neurodegenerative disease. PKC activity is rigorously fine-tuned by multiple mechanisms, but the spatial regulatory mechanism of PKC signaling remains fully understood. Here, we have shown that RNA granules, widely conserved non-membranous cytoplasmic structures composed of RNA-protein complexes, play a key role in spatially regulating PKC and its downstream MAPK signaling activation. Upon heat stress, PKC and downstream MAPK signaling activation was induced, which stimulates recruitment of the PKC homologue in fission yeast, from the plasma membrane into RNA granules. Intriguingly, Inhibition of the downstream MAPK signaling impaired PKC translocation to the RNA granules, whereas the constitutively active MAPKK stimulated PKC translocation to the RNA granules. We also demonstrated that the kinase activity of PKC influenced its intracellular distribution from the cell membranes to the RNA granules.  Our data is the first demonstration that PKC translocation into RNA granules is a novel feedback mechanism mediated by MAPK signaling.