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  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 & Development, 28, 1165-1178.

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 Creators:
Rosenbaum, Marc1, Author              
Andreani, Virginia2, Author
Kapoor, Tanya2, Author
Herp, Simone3, 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              
2Max Planck Society, ou_persistent13              
3Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              

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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.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 701945
 Degree: -

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Title: Genes & Development
Source Genre: Journal
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Pages: - Volume / Issue: 28 Sequence Number: - Start / End Page: 1165 - 1178 Identifier: -