Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Mol. Biol. Cell 12 (4): 957-969

Copyright © 2001 by The American Society for Cell Biology.

Vol. 12, Issue 4, 957-969, April 2001

Deletion of Yeast p24 Genes Activates the Unfolded Protein Response

William J. Belden, and Charles Barlowe*

Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755

Yeast cells lacking a functional p24 complex accumulate a subset of secretory proteins in the endoplasmic reticulum (ER) and increase the extracellular secretion of HDEL-containing ER residents such as Kar2p/BiP. We report that a loss of p24 function causes activation of the unfolded protein response (UPR) and leads to increased KAR2 expression. The HDEL receptor (Erd2p) is functional and traffics in p24 deletion strains as in wild-type strains, however the capacity of the retrieval pathway is exceeded. Other conditions that activate the UPR and elevate KAR2 expression also lead to extracellular secretion of Kar2p. Using an in vitro assay that reconstitutes budding from the ER, we detect elevated levels of Kar2p in ER-derived vesicles from p24 deletion strains and from wild-type strains with an activated UPR. Silencing the UPR by IRE1 deletion diminished Kar2p secretion under these conditions. We suggest that activation of the UPR plays a major role in extracellular secretion of Kar2p.

* Corresponding author. E-mail address: barlowe{at}

Molecular Biology of the Cell
Vol. 12, 957-969, April 2001
Copyright © 2001 by The American Society for Cell Biology

Isoform-selective Oligomer Formation of Saccharomyces cerevisiae p24 Family Proteins.
R. Hirata, C.-i. Nihei, and A. Nakano (2013)
J. Biol. Chem. 288, 37057-37070
   Abstract »    Full Text »    PDF »
The Endosomal Protein-Sorting Receptor Sortilin Has a Role in Trafficking {alpha}-1 Antitrypsin.
C. L. Gelling, I. W. Dawes, D. H. Perlmutter, E. A. Fisher, and J. L. Brodsky (2012)
Genetics 192, 889-903
   Abstract »    Full Text »    PDF »
Activation of the unfolded protein response pathway causes ceramide accumulation in yeast and INS-1E insulinoma cells.
S. Epstein, C. L. Kirkpatrick, G. A. Castillon, M. Muniz, I. Riezman, F. P. A. David, C. B. Wollheim, and H. Riezman (2012)
J. Lipid Res. 53, 412-420
   Abstract »    Full Text »    PDF »
Extracellular Secretion of Overexpressed Glycosylphosphatidylinositol-Linked Cell Wall Protein Utr2/Crh2p as a Novel Protein Quality Control Mechanism in Saccharomyces cerevisiae.
K. A. Miller, L. DiDone, and D. J. Krysan (2010)
Eukaryot. Cell 9, 1669-1679
   Abstract »    Full Text »    PDF »
Yet1p and Yet3p, the Yeast Homologs of BAP29 and BAP31, Interact with the Endoplasmic Reticulum Translocation Apparatus and Are Required for Inositol Prototrophy.
J. D. Wilson and C. Barlowe (2010)
J. Biol. Chem. 285, 18252-18261
   Abstract »    Full Text »    PDF »
Modeling a congenital disorder of glycosylation type I in C. elegans: A genome-wide RNAi screen for N-glycosylation-dependent loci.
W. B Struwe, B. L Hughes, D. W Osborn, E. D Boudreau, K. M D Shaw, and C. E Warren (2009)
Glycobiology 19, 1554-1562
   Abstract »    Full Text »    PDF »
Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control.
A. Copic, M. Dorrington, S. Pagant, J. Barry, M. C. S. Lee, I. Singh, J. L. Hartman IV, and E. A. Miller (2009)
Genetics 182, 757-769
   Abstract »    Full Text »    PDF »
Multicopy suppressor analysis of thermosensitive YIP1 alleles implicates GOT1 in transport from the ER.
A. Lorente-Rodriguez, M. Heidtman, and C. Barlowe (2009)
J. Cell Sci. 122, 1540-1550
   Abstract »    Full Text »    PDF »
Physical protein-protein interactions predicted from microarrays.
T.-t. Soong, K. O. Wrzeszczynski, and B. Rost (2008)
Bioinformatics 24, 2608-2614
   Abstract »    Full Text »    PDF »
The yeast p24 complex is required for the formation of COPI retrograde transport vesicles from the Golgi apparatus.
A. Aguilera-Romero, J. Kaminska, A. Spang, H. Riezman, and M. Muniz (2008)
J. Cell Biol. 180, 713-720
   Abstract »    Full Text »    PDF »
Pga1 Is an Essential Component of Glycosylphosphatidylinositol-Mannosyltransferase II of Saccharomyces cerevisiae.
K. Sato, Y. Noda, and K. Yoda (2007)
Mol. Biol. Cell 18, 3472-3485
   Abstract »    Full Text »    PDF »
Btn2, a Hook1 Ortholog and Potential Batten Disease-Related Protein, Mediates Late Endosome-Golgi Protein Sorting in Yeast.
R. Kama, M. Robinson, and J. E. Gerst (2007)
Mol. Cell. Biol. 27, 605-621
   Abstract »    Full Text »    PDF »
Inositol Deacylation by Bst1p Is Required for the Quality Control of Glycosylphosphatidylinositol-anchored Proteins.
M. Fujita, T. Yoko-o, and Y. Jigami (2006)
Mol. Biol. Cell 17, 834-850
   Abstract »    Full Text »    PDF »
Overexpression of an Anti-CD3 Immunotoxin Increases Expression and Secretion of Molecular Chaperone BiP/Kar2p by Pichia pastoris.
Y. Y. Liu, J. H. Woo, and D. M. Neville Jr. (2005)
Appl. Envir. Microbiol. 71, 5332-5340
   Abstract »    Full Text »    PDF »
Immunoisolaton of the Yeast Golgi Subcompartments and Characterization of a Novel Membrane Protein, Svp26, Discovered in the Sed5-Containing Compartments.
H. Inadome, Y. Noda, H. Adachi, and K. Yoda (2005)
Mol. Cell. Biol. 25, 7696-7710
   Abstract »    Full Text »    PDF »
PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis.
T. Simmen, J. E. Aslan, A. D. Blagoveshchenskaya, L. Thomas, L. Wan, Y. Xiang, S. F. Feliciangeli, C.-H. Hung, C. M. Crump, and G. Thomas (2005)
EMBO J. 24, 717-729
   Abstract »    Full Text »    PDF »
Genetic Analysis of Yeast Yip1p Function Reveals a Requirement for Golgi-Localized Rab Proteins and Rab-Guanine Nucleotide Dissociation Inhibitor.
C. Z. Chen, M. Calero, C. J. DeRegis, M. Heidtman, C. Barlowe, and R. N. Collins (2004)
Genetics 168, 1827-1841
   Abstract »    Full Text »    PDF »
Role of the Unfolded Protein Response Pathway in Secretory Stress and Regulation of INO1 Expression in Saccharomyces cerevisiae.
H. J. Chang, S. A. Jesch, M. L. Gaspar, and S. A. Henry (2004)
Genetics 168, 1899-1913
   Abstract »    Full Text »    PDF »
A Cell-Specific Transgenic Approach in Xenopus Reveals the Importance of a Functional p24 System for a Secretory Cell.
G. Bouw, R. Van Huizen, E. J.R. Jansen, and G. J.M. Martens (2004)
Mol. Biol. Cell 15, 1244-1253
   Abstract »    Full Text »    PDF »
The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics.
G. Emery, R. G. Parton, M. Rojo, and J. Gruenberg (2003)
J. Cell Sci. 116, 4821-4832
   Abstract »    Full Text »    PDF »
A role for Yip1p in COPII vesicle biogenesis.
M. Heidtman, C. Z. Chen, R. N. Collins, and C. Barlowe (2003)
J. Cell Biol. 163, 57-69
   Abstract »    Full Text »    PDF »
Genetic Analysis of Caenorhabditis elegans glp-1 Mutants Suggests Receptor Interaction or Competition.
A. S.-R. Pepper, D. J. Killian, and E. J. A. Hubbard (2003)
Genetics 163, 115-132
   Abstract »    Full Text »    PDF »
The Erv41p-Erv46p complex: multiple export signals are required in trans for COPII-dependent transport from the ER.
S. Otte and C. Barlowe (2002)
EMBO J. 21, 6095-6104
   Abstract »    Full Text »    PDF »
YOS9, the Putative Yeast Homolog of a Gene Amplified in Osteosarcomas, Is Involved in the Endoplasmic Reticulum (ER)-Golgi Transport of GPI-anchored Proteins.
E. Friedmann, Y. Salzberg, A. Weinberger, S. Shaltiel, and J. E. Gerst (2002)
J. Biol. Chem. 277, 35274-35281
   Abstract »    Full Text »    PDF »
Analysis of Sec22p in Endoplasmic Reticulum/Golgi Transport Reveals Cellular Redundancy in SNARE Protein Function.
Y. Liu and C. Barlowe (2002)
Mol. Biol. Cell 13, 3314-3324
   Abstract »    Full Text »    PDF »
ER-Golgi Traffic Is a Prerequisite for Efficient ER Degradation.
C. Taxis, F. Vogel, and D. H. Wolf (2002)
Mol. Biol. Cell 13, 1806-1818
   Abstract »    Full Text »    PDF »
Golgi-to-Endoplasmic Reticulum (ER) Retrograde Traffic in Yeast Requires Dsl1p, a Component of the ER Target Site that Interacts with a COPI Coat Subunit.
B. A. Reilly, B. A. Kraynack, S. M. VanRheenen, and M. G. Waters (2001)
Mol. Biol. Cell 12, 3783-3796
   Abstract »    Full Text »    PDF »
Distinct Roles for the Cytoplasmic Tail Sequences of Emp24p and Erv25p in Transport between the Endoplasmic Reticulum and Golgi Complex.
W. J. Belden and C. Barlowe (2001)
J. Biol. Chem. 276, 43040-43048
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882