Co-chaperones of the Mammalian Endoplasmic Reticulum - The Networking of Chaperones by Co-chaperones - page 177

Chapter 9
Co-chaperones of the Mammalian Endoplasmic
Reticulum

Armin Melnyk, Heiko Rieger and Richard Zimmermann

Abstract In mammalian cells, the rough endoplasmic reticulum or ER plays a cen-
tral role in the biogenesis of most extracellular plus many organellar proteins and in
cellular calcium homeostasis. Therefore, this organelle comprises molecular chaper-
ones that are involved in import, folding/assembly, export, and degradation of poly-
peptides in millimolar concentrations. In addition, there are calcium channels/pumps
and signal transduction components present in the ER membrane that affect and are
affected by these processes. The ER lumenal Hsp70, termed immunoglobulin-heavy
chain binding protein or BiP, is the central player in all these activities and involves
up to seven different co-chaperones, i.e. ER-membrane integrated as well as ER-
lumenal Hsp40s, which are termed ERj or ERdj, and two nucleotide exchange factors.

Keywords Human endoplasmic reticulum ﾷ Cellular calcium hoemostasis ﾷ Protein
transport ﾷ Protein folding ﾷ Protein degradation

Introduction

In all nucleated human cells the endoplasmic reticulum or ER forms a vast and dy-
namic membrane network (Palade 1975 ; English and Voeltz 2013 ). The rough ER
is studded with 80S ribosomes. These ribosomes are engaged in the biosynthesis of
most secretory and many organellar proteins by cotranslationally inserting nascent
polypeptides into the membrane and lumen of the ER, thus defining one major func-
tion of the rough ER. The peripheral ER contacts the plasma membrane, the tubular
ER contacts mitochondria (Kornmann et al. 2009 ; Hayashi et al. 2009 ; Bakowski