Study on the osmo-sensing mechanism in yeast

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04761
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Tatebayashi Kazuo 東京大学, 医科学研究所, 准教授 (50272498)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 高浸透圧 / 酵母 / MAP kinase経路 / センサー / シグナル伝達 / リン酸化

Outline of Final Research Achievements

The MAP kinase (MAPK) Hog1 is the central regulator of osmoadaptation in yeast. Upon high osmolarity, the Sho1 and Sln1 membrane-associated osmosensors, respectively, activate the Ste11-Pbs2-Hog1 MAPK cascade and the Ssk2/Ssk22-Pbs2-Hog1 MAPK cascade. Sho1 binds to several transmembrane proteins such as Opy2 to form an osmo-sensing protein complex for transduction of an activating signal. In this work, we identified two binding sites between Sho1 and Opy2, and found that the Sho1-Opy2 interaction enhances the signaling efficiency from Ste11 MAPKKK to Pbs2 MAPKK. In addition, we found that the Hog1 MAPK phosphorylation by Pbs2 MAPKK is enhanced by high osmolarity independently of the membrane-associated osmosensors. The lack of the osmotic enhancement of the Pbs2-Hog1 reaction suppresses Hog1 activation by basal MAP3K activities and prevents pheromone-to-Hog1 crosstalk in the absence of osmostress, which enable the yeast cells to respond appropriately to environmental stresses.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかになった膜タンパク質型及び非膜タンパク質型の高浸透圧センサーを介した高浸透圧応答制御機構は、適切な環境ストレス応答を保障する仕組みとしてヒトなどの高等真核生物にも当てはまる可能性が高い。今後の検証を通じて、環境ストレス応答制御の全体像の理解や、環境ストレス耐性の動植物への付与技術の開発などに繋がることが期待される。また本研究で解明されたHog1 MAPKの制御機構に関する知見は、ヒトMAPKの制御破綻が引き起こす癌や自己免疫疾患といった疾患の治療法・治療薬の開発にも役立つと考えられる。