EMAIL THIS PAGE TO A FRIEND

The Journal of neuroscience : the official journal of the Society for Neuroscience

ER Chaperone BiP/GRP78 Is Required for Myelinating Cell Survival and Provides Protection during Experimental Autoimmune Encephalomyelitis.


PMID 26631473

Abstract

Myelinating cells synthesize large amounts of membrane protein through the secretory pathway, which makes these cells particularly sensitive to perturbations of the endoplasmic reticulum (ER). Ig binding protein (BiP), also known as glucose-regulated protein 78 (GRP78), is a critical ER chaperone that also plays a pivotal role in controlling the cellular response to ER stress. To examine the potential importance of BiP to myelinating cells, we used a conditional knock-out approach to BiP gene inactivation in oligodendrocytes during development, in adulthood, and in response to experimental autoimmune encephalomyelitis (EAE), an animal model of the inflammatory demyelinating disorder multiple sclerosis (MS). During development, mice lacking functional BiP gene expression in oligodendrocytes developed tremors and ataxia and died before reaching maturity. When BiP gene inactivation in oligodendrocytes was initiated in adulthood, the mice displayed severe neurological symptoms including tremors and hind-limb paralysis. The inactivation of BiP in oligodendrocytes during development or in adulthood resulted in oligodendrocyte loss and corresponding severe myelin abnormalities. Mice heterozygous for the oligodendrocyte-specific inactivation of BiP, which were phenotypically normal without evidence of neuropathology, displayed an exacerbated response to EAE that correlated with an increased loss of oligodendrocytes. Furthermore, mice in which the BiP gene was specifically inactivated in developing Schwann cells displayed tremor that progressed to hindlimb paralysis, which correlated with diminished numbers of myelinating Schwann cells and severe PNS hypomyelination. These studies demonstrate that BiP is critical for myelinating cell survival and contributes to the protective response of oligodendrocyte against inflammatory demyelination.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

PRS3681
Anti-ATF6 (ab1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
PRS3683
Anti-ATF6 (ab2) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1400432
Anti-ATF6 antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
SAB2100170
Anti-ATF6 antibody produced in rabbit, affinity isolated antibody
HPA005935 Anti-ATF6 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2106254
Anti-ATF6 antibody produced in rabbit, affinity isolated antibody
SAB1405706
Anti-DDIT3 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB4500632
Anti-GADD153 antibody produced in rabbit, affinity isolated antibody
SAB2100885
Anti-GALC antibody produced in rabbit, affinity isolated antibody
SAB1410476
Anti-GALC antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1401236
Anti-MAG antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA012499
Anti-MAG antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1402546
Monoclonal Anti-ATF6 antibody produced in mouse, clone 3D5, purified immunoglobulin, buffered aqueous solution
WH0001649M1
Monoclonal Anti-DDIT3 antibody produced in mouse, clone 2G3, purified immunoglobulin, buffered aqueous solution
SAB1403729
Monoclonal Anti-DDIT3 antibody produced in mouse, clone 2C4, purified immunoglobulin, buffered aqueous solution
SAB1402780
Monoclonal Anti-GALC, (C-terminal) antibody produced in mouse, clone 2D1, purified immunoglobulin, buffered aqueous solution
SAB1402258
Monoclonal Anti-MAG antibody produced in mouse, clone 3C7, purified immunoglobulin, buffered aqueous solution
P9255
Pyridoxal 5′-phosphate hydrate, ≥98%
C8H10NO6P · xH2O
P3657
Pyridoxal 5′-phosphate hydrate, powder, BioReagent, suitable for cell culture
C8H10NO6P · xH2O
82870
Pyridoxal 5′-phosphate monohydrate, ≥97.0% (NT)
C8H10NO6P · H2O