GRP78: a chaperone with diverse roles beyond the endoplasmic reticulum.

Published

Journal Article (Review)

Glucose-regulated protein 78 (GRP78) is a well-characterized molecular chaperone that is ubiquitously expressed in mammalian cells. GRP78 is best known for binding to hydrophobic patches on nascent polypeptides within the endoplasmic reticulum (ER) and for its role in signaling the unfolded protein response. Structurally, GRP78 is highly conserved across species. The presence of GRP78 or a homologue in nearly every organism from bacteria to man, reflects the central roles it plays in cell survival. While the principal role of GRP78 as a molecular chaperone is a matter of continuing study, independent work demonstrates that like many other proteins with ancient origins, GRP78 plays more roles than originally appreciated. Studies have shown that GRP78 is expressed on the cell surface in many tissue types both in vitro and in vivo. Cell surface GRP78 is involved in transducing signals from ligands as disparate as activated alpha2-macroglobulin and antibodies. Plasmalemmar GRP78 also plays a role in viral entry of Coxsackie B, and Dengue Fever viruses. GRP78 disregulation is also implicated in atherosclerotic, thrombotic, and auto-immune disease. It is challenging to posit a hypothesis as to why an ER molecular chaperone, such as GRP78, plays such a variety of roles in cellular processes. An ancient and highly conserved protein such as GRP78, whose primary function is to bind to misfolded polypeptides, could be uniquely suited to bind a wide variety of ligands and thus, over time, could assume the wide variety of roles it now plays.

Full Text

Duke Authors

Cited Authors

  • Quinones, QJ; de Ridder, GG; Pizzo, SV

Published Date

  • November 2008

Published In

Volume / Issue

  • 23 / 11

Start / End Page

  • 1409 - 1416

PubMed ID

  • 18785123

Pubmed Central ID

  • 18785123

Electronic International Standard Serial Number (EISSN)

  • 1699-5848

Digital Object Identifier (DOI)

  • 10.14670/HH-23.1409

Language

  • eng

Conference Location

  • Spain