A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum.
Protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus is mediated by transport vesicles coated with the coat protein complex II (COPII). In the process of searching for novel factors that participate in the formation of COPII-coated vesicles (COPII vesicles), we isolated high-copy suppressors of a sec24-20 mutant defective in COPII vesicle formation from the ER at the restrictive temperature. Unexpectedly, one of them was identified as HAC1, a gene encoding the basic leucine-zipper type transcription factor Hac1p. Hac1p is essential for a signaling cascade activated by ER stress, termed the unfolded protein response (UPR) pathway, that leads from the ER to the nucleus. Overexpression of another UPR-related gene IRE1, which encodes an ER-resident transmembrane protein kinase/ribonuclease, also suppressed the growth defect of the sec24-20 mutant in a HAC1-dependent manner. Moreover, overexpression of IRE1 specifically suppressed growth defects of other sec mutants defective in COPII vesicle formation. These findings suggest that the activation of the UPR affects ER-to-Golgi transport via stimulation of COPII vesicle formation from the ER.
Higashio
Hironori
H
Research and Education Center for Genetic Information, Nara Institute of Science and Technology (NAIST), Takayama, Ikoma, Nara 630-0101, Japan.
Kohno
Kenji
K
D050976:Basic-Leucine Zipper Transcription Factors; D022181:COP-Coated Vesicles / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016153:Genes, Suppressor; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D012331:RNA, Fungal / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors
D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012331:RNA, Fungal; D012097:Repressor Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases