Glucose‐regulated protein (GRP78) is an important cell surface receptor for viral invasion, cancers, and neurological disorders

Abstract

The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellular stress, GRP78 escapes from the ER and moves to the plasma membrane where it (a) functions as a receptor for many ligands, and (b) behaves as an autoantigen for autoantibodies that contribute to human disease and cancer. Cell surface GRP78 (csGRP78) associates with the major histocompatibility complex class I (MHC-I), and is the port of entry for several viruses, including the predictive binding of the novel SARS-CoV-2. Furthermore, csGRP78 is found in association with partners as diverse as the teratocarcinoma-derived growth factor 1 (Cripto), the melanocortin-4 receptor (MC4R) and the DnaJ-like protein MTJ-1. CsGRP78 also serves as a receptor for a large variety of ligands including activated α 2 -macroglobulin (α 2 M*), plasminogen kringle 5 (K5), microplasminogen, the voltage-dependent anion channel (VDAC), tissue factor (TF), and the prostate apoptosis response-4 protein (Par-4). In this review, we discuss the mechanisms involved in the translo-

An Endogenous Retroviral LTR-Derived Long Noncoding RNA lnc-LTR5B Interacts With BiP to Modulate ALV-J Replication in Chicken Cells

“…However, the expression levels of cell surface BiP are generally considered to be low under normal physiological conditions. The translocation of BiP to the cell surface can be observed under conditions of cellular stress, including viral infection ( Gonzalez-Gronow et al, 2021 ). To examine whether ALV-J infection induces the translocation of BiP to the DF-1 cell surface, we performed immunocytochemical staining to analyze the distribution patterns of BiP in both permeabilized and non-permeabilized cells ( Figure 5 ).…”

Commentary: A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19. A Metabolic Endocrinology Perspective

“…A role for GRP78 in COVID-19 had already been implicated with evidence that the SARS-CoV-2 Spike-protein binds to GRP78 and that viral entry and replication within host cells could be suppressed by inhibition ( 60 ) or depletion of GRP78 ( 61 ). Indeed, many viruses appear to hijack GRP78 to infect human cells ( 62 ). This common mechanism for cell invasion provides a link explaining the importance of hyperglycemia in both the COVID-19 and mucormycosis pandemics ( 51 – 53 ) and demonstrates the broader implications of the AI generated insights into how hyperglycemia affects the internal milieu ( 5 ).…”

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

“…An intracellular ER stress increase may upregulate the GRP78 expression and induce GRP78 re-localization to the cell membrane as cell surface GRP78 ( Elfiky et al, 2021 ). The cellular surface GRP78 can associate with the major histocompatibility complex class I (MHC-I) that may aid SARS-CoV-2 to get into the host cells for starting an infection or help viral release from infected host cells ( Ha et al, 2020 ; Gonzalez-Gronow et al, 2021 ). In silico data showed curcumin could interact with the S protein binding site and ATPase domain of GRP78 ( Allam et al, 2020 ; Sudeep et al, 2020 ), suggesting that curcumin can assist in preventing COVID-19 viral attachment and enter host cells by binding to and inhibiting GRP78 of host cell surface.…”