GRP94 in ER Quality Control and Stress Responses

Overview

Journal Semin Cell Dev Biol

Specialties Cell Biology
Reproductive Medicine

Date 2010 Mar 13

PMID 20223290

Citations 110

Authors

Davide Eletto

Devin Dersh

Yair Argon

Affiliations

Soon will be listed here.

Abstract

A system of endoplasmic reticulum (ER) chaperones has evolved to optimize the output of properly folded secretory and membrane proteins. An important player in this network is Glucose Regulated Protein 94 (GRP94). Over the last decade, new structural and functional data have begun to delineate the unique characteristics of GRP94 and have solidified its importance in ER quality control pathways. This review describes our current understanding of GRP94 and the four ways in which it contributes to the ER quality control: (1) chaperoning the folding of proteins; (2) interacting with other components of the ER protein folding machinery; (3) storing calcium; and (4) assisting in the targeting of malfolded proteins to ER-associated degradation (ERAD).

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References

Gidalevitz T, Biswas C, Ding H, Schneidman-Duhovny D, Wolfson H, Stevens F . Identification of the N-terminal peptide binding site of glucose-regulated protein 94. J Biol Chem. 2004; 279(16):16543-52. DOI: 10.1074/jbc.M313060200. View

Immormino R, Dollins D, Shaffer P, Soldano K, Walker M, Gewirth D . Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone. J Biol Chem. 2004; 279(44):46162-71. DOI: 10.1074/jbc.M405253200. View

Shiu R, Pouyssegur J, Pastan I . Glucose depletion accounts for the induction of two transformation-sensitive membrane proteinsin Rous sarcoma virus-transformed chick embryo fibroblasts. Proc Natl Acad Sci U S A. 1977; 74(9):3840-4. PMC: 431753. DOI: 10.1073/pnas.74.9.3840. View

Drummond I, Lee A, Resendez Jr E, Steinhardt R . Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts. J Biol Chem. 1987; 262(26):12801-5. View

Macer D, Koch G . Identification of a set of calcium-binding proteins in reticuloplasm, the luminal content of the endoplasmic reticulum. J Cell Sci. 1988; 91 ( Pt 1):61-70. DOI: 10.1242/jcs.91.1.61. View

Chang S, Erwin A, Lee A . Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors. Mol Cell Biol. 1989; 9(5):2153-62. PMC: 363009. DOI: 10.1128/mcb.9.5.2153-2162.1989. View

Van P, Peter F, SOLING H . Four intracisternal calcium-binding glycoproteins from rat liver microsomes with high affinity for calcium. No indication for calsequestrin-like proteins in inositol 1,4,5-trisphosphate-sensitive calcium sequestering rat liver vesicles. J Biol Chem. 1989; 264(29):17494-501. View

Wiest D, Burkhardt J, Hester S, Hortsch M, Meyer D, Argon Y . Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol. 1990; 110(5):1501-11. PMC: 2200180. DOI: 10.1083/jcb.110.5.1501. View

Kang H, Welch W . Characterization and purification of the 94-kDa glucose-regulated protein. J Biol Chem. 1991; 266(9):5643-9. View

10.

Baksh S, Michalak M . Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. J Biol Chem. 1991; 266(32):21458-65. View

11.

Nakanishi K, Sudo T, Morishima N . Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development. J Cell Biol. 2005; 169(4):555-60. PMC: 2171703. DOI: 10.1083/jcb.200412024. View

12.

Kapulkin W, Kapulkin V, Hiester B, Link C . Compensatory regulation among ER chaperones in C. elegans. FEBS Lett. 2005; 579(14):3063-8. DOI: 10.1016/j.febslet.2005.04.062. View

13.

Dollins D, Immormino R, Gewirth D . Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for nucleotide-induced conformational change. J Biol Chem. 2005; 280(34):30438-47. DOI: 10.1074/jbc.M503761200. View

14.

Bhamidipati A, Denic V, Quan E, Weissman J . Exploration of the topological requirements of ERAD identifies Yos9p as a lectin sensor of misfolded glycoproteins in the ER lumen. Mol Cell. 2005; 19(6):741-51. DOI: 10.1016/j.molcel.2005.07.027. View

15.

Kim W, Spear E, Ng D . Yos9p detects and targets misfolded glycoproteins for ER-associated degradation. Mol Cell. 2005; 19(6):753-64. DOI: 10.1016/j.molcel.2005.08.010. View

16.

Szathmary R, Bielmann R, Nita-Lazar M, Burda P, Jakob C . Yos9 protein is essential for degradation of misfolded glycoproteins and may function as lectin in ERAD. Mol Cell. 2005; 19(6):765-75. DOI: 10.1016/j.molcel.2005.08.015. View

17.

Yang Y, Li Z . Roles of heat shock protein gp96 in the ER quality control: redundant or unique function?. Mol Cells. 2005; 20(2):173-82. View

18.

Srivastava P . Therapeutic cancer vaccines. Curr Opin Immunol. 2006; 18(2):201-5. DOI: 10.1016/j.coi.2006.01.009. View

19.

Snapp E, Sharma A, Lippincott-Schwartz J, Hegde R . Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cells. Proc Natl Acad Sci U S A. 2006; 103(17):6536-41. PMC: 1458919. DOI: 10.1073/pnas.0510657103. View

20.

Chu F, Maynard J, Chiosis G, Nicchitta C, Burlingame A . Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94. Protein Sci. 2006; 15(6):1260-9. PMC: 2242539. DOI: 10.1110/ps.052065106. View