The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane.
Yeast cells sense alterations in the plasma membrane (PM) lipid asymmetry and external alkalization by the sensor protein Rim21, which functions in the Rim101 pathway. Rim101 signaling is initiated at the PM by the recruitment of the Rim101 signaling complex. The PM physically associates with the cortical endoplasmic reticulum (ER) to form ER-PM contact sites, where several signaling events, lipid exchange, and ion transport take place. In the present study, we investigated the spatial relationship between ER-PM contact sites and the sites of Rim101 signaling. Rim101 signaling mostly proceeds outside ER-PM contact sites in the PM and did not require intact ER-PM contact for its activation. Rather, the Rim101 pathway was constitutively activated by ER-PM contact site disruption, which is known to cause ER stress. ER stress induced by tunicamycin treatment activated the Rim101 pathway. Furthermore, the sensitivity of cells to tunicamycin without ER-PM contact was considerably elevated by the deletion of RIM21. These results suggest that the Rim101 pathway is important for the adaptation to ER stress by compensating for alterations in PM lipid asymmetry induced by ER stress.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.
Keisuke
K
Obara
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan kihara@pharm.hokudai.ac.jp.
Akio
A
Kihara
D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014415:Tunicamycin / Q000494:pharmacology
C489601:RIM101 protein, S cerevisiae; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C547025:Rim21 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014415:Tunicamycin
ER stress; Rim101 pathway; Saccharomyces cerevisiae; contact site; lipid asymmetry; plasma membrane