The mechanism of osmo-regulatory signal transduction by interactions among membrane proteins through their TM regions

2014 Fiscal Year Final Research Report

• Project/Area Number: 24247034
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: SAITO Haruo 東京大学, 医科学研究所, 教授 (60114485)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Signal transduction / Yeast / Osmoregulation / Membrane protein / MAP kinase

Outline of Final Research Achievements

When exposed to hyperosmolarity, the budding yeast Saccharomyces cerevisiae activates the Hog1 MAP kinase signal pathway, which governs an array of adaptive responses. In this project, we investigated how the activity of the Hog1 MAPK pathway is regulated by the Sho1 osmosensor and the Hkr1/Msb2 co-osmosensors. First, we determined the oligomeric structure of the 4TM osmosensor Sho1 using a site-directed chemical crosslinking strategy. External osmolarity influenced the internal structure of the Sho1 oligomer as well as the interactions between the Sho1 oligomers and cytoplasmic signaling proteins. Second, we found that specific and dynamic bindings of the Hkr1/Msb2 co-osmosensors to the membrane anchorage protein Opy2 and to cytoplasmic scaffold proteins are essential for Hog1 activation. From these results, details of the mechanism of Hog1 activation by external high osmolarity are revealed.

Free Research Field

Molecular Cell Biology