This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Afshar, N.
Right arrow Articles by Paschal, B. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Afshar, N.
Right arrow Articles by Paschal, B. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2005, p. 8844-8853, Vol. 25, No. 20
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.20.8844-8853.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Retrotranslocation of the Chaperone Calreticulin from the Endoplasmic Reticulum Lumen to the Cytosol

Nima Afshar, Ben E. Black,{dagger} and Bryce M. Paschal*

Center for Cell Signaling and Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908

Received 28 June 2005/ Returned for modification 12 July 2005/ Accepted 20 July 2005

Polypeptide folding and quality control in the endoplasmic reticulum (ER) are mediated by protein chaperones, including calreticulin (CRT). ER localization of CRT is specified by two types of targeting signals, an N-terminal hydrophobic signal sequence that directs insertion into the ER and a C-terminal KDEL sequence that is responsible for retention in the ER. CRT has been implicated in a number of cytoplasmic and nuclear processes, suggesting that there may be a pathway for generating cytosolic CRT. Here we show that CRT is fully inserted into the ER, undergoes processing by signal peptidase, and subsequently undergoes retrotranslocation to the cytoplasm. A transcription-based reporter assay revealed an important role for the C-terminal Ca2+ binding domain in CRT retrotranslocation. Neither ubiquitylation nor proteasome activity was necessary for retrotranslocation, which indicates that the pathway is different from that used by unfolded proteins targeted for destruction. Forced expression of cytosolic CRT is sufficient to rescue a cell adhesion defect observed in mouse embryo fibroblasts from crt–/– mice. The ability of CRT to retrotranslocate from the ER lumen to the cytosol explains how CRT can change compartments and modulate cell adhesion, transcription, and translation.

* Corresponding author. Mailing address: Center for Cell Signaling, Box 800577 Health Systems, University of Virginia, Charlottesville, VA 22908. Phone: 434-243-6521. Fax: 434-924-1236. E-mail: paschal{at}virginia.edu.

{dagger} Present address: Ludwig Institute for Cancer Research and Department of Cellular Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.

Molecular and Cellular Biology, October 2005, p. 8844-8853, Vol. 25, No. 20
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.20.8844-8853.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Leichner, G. S., Avner, R., Harats, D., Roitelman, J. (2009). Dislocation of HMG-CoA Reductase and Insig-1, Two Polytopic Endoplasmic Reticulum Proteins, En Route to Proteasomal Degradation. Mol. Biol. Cell 20: 3330-3341 [Abstract] [Full Text]  
  • Grespin, M. E., Bonamy, G. M. C., Roggero, V. R., Cameron, N. G., Adam, L. E., Atchison, A. P., Fratto, V. M., Allison, L. A. (2008). Thyroid Hormone Receptor {alpha}1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway. J. Biol. Chem. 283: 25576-25588 [Abstract] [Full Text]  
  • Surjit, M., Jameel, S., Lal, S. K. (2007). Cytoplasmic Localization of the ORF2 Protein of Hepatitis E Virus Is Dependent on Its Ability To Undergo Retrotranslocation from the Endoplasmic Reticulum. J. Virol. 81: 3339-3345 [Abstract] [Full Text]  
  • Decca, M. B., Carpio, M. A., Bosc, C., Galiano, M. R., Job, D., Andrieux, A., Hallak, M. E. (2007). Post-translational Arginylation of Calreticulin: A NEW ISOSPECIES OF CALRETICULIN COMPONENT OF STRESS GRANULES. J. Biol. Chem. 282: 8237-8245 [Abstract] [Full Text]  
  • Hayashida, Y., Urata, Y., Muroi, E., Kono, T., Miyata, Y., Nomata, K., Kanetake, H., Kondo, T., Ihara, Y. (2006). Calreticulin Represses E-cadherin Gene Expression in Madin-Darby Canine Kidney Cells via Slug. J. Biol. Chem. 281: 32469-32484 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»