Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP

Yi Zhang, Ren Liu, Min Ni, Parkash Gill, Amy S. Lee

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

The recent discovery that GRP78/BiP, a typical endoplasmic reticulum (ER) lumenal chaperone, can be expressed on the cell surface, interacting with an increasing repertoire of surface proteins and acting as receptor in signaling pathways, represents a paradigm shift in its biological function. However, the mechanism of GRP78 trafficking from the ER to the cell surface is not well understood. Using a combination of cellular, biochemical, and mutational approaches, we tested multiple hypotheses. Here we report that ER stress actively promotes GRP78 localization on the cell surface, whereas ectopic expression of GRP78 is also able to cause cell surface relocation in the absence of ER stress. Moreover, deletion of the C-terminal ER retention motif in GRP78 alters its cell surface presentation in a dose-dependent manner; however, mutation of the putative O-linked glycosylation site Thr648 of human GRP78 is without effect.We also identified the exposure of multiple domains of GRP78 on the cell surface and determined that binding of extracellular GRP78 to the cell surface is unlikely. A new topology model for cell surface GRP78 is presented.

Original languageEnglish (US)
Pages (from-to)15065-15075
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number20
DOIs
StatePublished - May 14 2010

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Unfolded Protein Response
Endoplasmic Reticulum
Proteins
Endoplasmic Reticulum Stress
Glycosylation
Relocation
Membrane Proteins
Topology
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP. / Zhang, Yi; Liu, Ren; Ni, Min; Gill, Parkash; Lee, Amy S.

In: Journal of Biological Chemistry, Vol. 285, No. 20, 14.05.2010, p. 15065-15075.

Research output: Contribution to journalArticle

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