English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

Rosenbaum, M., Andreani, V., Kapoor, T., Herp, S., Flach, H., Duchniewicz, M., et al. (2014). MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress. Genes and Development, 28, 1165-1178. doi:10.1101/gad.240762.114.

Item is

Files

show Files
hide Files
:
Rosenbaum 2014_Genes Dev.pdf (Publisher version), 3MB
 
File Permalink:
-
Name:
Rosenbaum 2014_Genes Dev.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute of Immunobiology and Epigenetics, MFIB; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Locator:
http://genesdev.cshlp.org/content/28/11/1165 (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Rosenbaum, Marc1, Author              
Andreani, Virginia1, Author
Kapoor, Tanya1, Author
Herp, Simone1, Author              
Flach, Henrik1, Author              
Duchniewicz, Marlena1, Author              
Grosschedl, Rudolf1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

Content

show
hide
Free keywords: MZB1; B lymphopoiesis; antibody secretion; ER stress; GRP94; cochaperone
 Abstract: MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1-/- mice. A similar developmental block was observed in Mzb1fl/flmb1Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin µ heavy chains (µHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with µHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of µHCs under conditions of ER stress.

Details

show
hide
Language(s): eng - English
 Dates: 2014-06-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1101/gad.240762.114
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Genes and Development
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 28 Sequence Number: - Start / End Page: 1165 - 1178 Identifier: ISSN: 0890-9369
CoNE: https://pure.mpg.de/cone/journals/resource/954925557453