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Co-chaperones of the Human Endoplasmic Reticulum: An Update

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The Networking of Chaperones by Co-Chaperones

Part of the book series: Subcellular Biochemistry ((SCBI,volume 101))

Abstract

In mammalian cells, the rough endoplasmic reticulum (ER) plays central roles in the biogenesis of extracellular plus organellar proteins and in various signal transduction pathways. For these reasons, the ER comprises molecular chaperones, which are involved in import, folding, assembly, export, plus degradation of polypeptides, and signal transduction components, such as calcium channels, calcium pumps, and UPR transducers plus adenine nucleotide carriers/exchangers in the ER membrane. The calcium- and ATP-dependent ER lumenal Hsp70, termed immunoglobulin heavy-chain-binding protein or BiP, is the central player in all these activities and involves up to nine different Hsp40-type co-chaperones, i.e., ER membrane integrated as well as ER lumenal J-domain proteins, termed ERj or ERdj proteins, two nucleotide exchange factors or NEFs (Grp170 and Sil1), and NEF-antagonists, such as MANF. Here we summarize the current knowledge on the ER-resident BiP/ERj chaperone network and focus on the interaction of BiP with the polypeptide-conducting and calcium-permeable Sec61 channel of the ER membrane as an example for BiP action and how its functional cycle is linked to ER protein import and various calcium-dependent signal transduction pathways.

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Acknowledgments

This review is dedicated to the memory of Dr Thomas Dierks (Bielefeld, Germany), who established the reconstitution of BiP and Grp170 together with microsomal membrane proteins into proteoliposomes in our lab in Göttingen in 1995. We are grateful to Anke Ziska (Homburg) for cloning the novel BiP variants and to Drs Thorsten Möhlmann and Ekkehard Neuhaus (both Technical University Kaiserslautern, Kaiserslautern, Germany) for giving us access to their BIACORE 2000 system. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) within the framework of the International Research Training Group 1830.

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  1. Medical Biochemistry & Molecular Biology, Saarland University, Homburg, Germany

    Armin Melnyk, Sven Lang, Mark Sicking, Richard Zimmermann & Martin Jung

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  1. Armin Melnyk
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  2. Sven Lang
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Correspondence to Richard Zimmermann .

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  1. Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa

    Adrienne L. Edkins

  2. Faculty of Health Sciences, Higher Colleges of Technology, Sharjah, United Arab Emirates

    Gregory L. Blatch

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Melnyk, A., Lang, S., Sicking, M., Zimmermann, R., Jung, M. (2023). Co-chaperones of the Human Endoplasmic Reticulum: An Update. In: Edkins, A.L., Blatch, G.L. (eds) The Networking of Chaperones by Co-Chaperones. Subcellular Biochemistry, vol 101. Springer, Cham. https://doi.org/10.1007/978-3-031-14740-1_9

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