title: Osmosensing and scaffolding functions of the oligomeric four-transmembrane domain osmosensor Sho1.
abstract: The yeast high osmolarity glycerol (HOG) pathway activates the Hog1 MAP kinase, which coordinates adaptation to high osmolarity conditions. Here we demonstrate that the four-transmembrane (TM) domain protein Sho1 is an osmosensor in the HKR1 sub-branch of the HOG pathway. Crosslinking studies indicate that Sho1 forms planar oligomers of the dimers-of-trimers architecture by dimerizing at the TM1/TM4 interface and trimerizing at the TM2/TM3 interface. High external osmolarity induces structural changes in the Sho1 TM domains and Sho1 binding to the cytoplasmic adaptor protein Ste50, which leads to Hog1 activation. Besides its osmosensing function, the Sho1 oligomer serves as a scaffold. By binding to the TM proteins Opy2 and Hkr1 at the TM1/TM4 and TM2/TM3 interface, respectively, Sho1 forms a multi-component signalling complex that is essential for Hog1 activation. Our results illuminate how the four TM domains of Sho1 dictate the oligomer structure as well as its osmosensing and scaffolding functions.
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tatebayashi
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Nagoya
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Momma
authors.affiliation: Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Saito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009997:Osmotic Pressure; D010957:Plasmids; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C459787:SHO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins