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. 2020 Sep 8:11:574339.
doi: 10.3389/fphys.2020.574339. eCollection 2020.

The Probable, Possible, and Novel Functions of ERp29

Margaret Brecker  1 , Svetlana Khakhina  1 , Tyler J Schubert  1 , Zachary Thompson  1 , Ronald C Rubenstein  1   2   3
Affiliations

The Probable, Possible, and Novel Functions of ERp29

Margaret Brecker et al. Front Physiol. .

Abstract

The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to cis-Golgi cargo protein transport via COP II machinery through its interactions with the KDEL receptor; this interaction may facilitate the loading of ERp29 clients into COP II vesicles. ERp29 also plays a role in ER stress (ERS) and the unfolded protein response (UPR) and is implicated in oncogenesis. Here, we review the vast array of ERp29's clients, its role as an ER to Golgi escort protein, and further suggest ERp29 as a potential target for therapies related to diseases of protein misfolding and mistrafficking.

Keywords: COP II; ERp29; Golgi; chaperone; endoplasmic reticulum; escort; secretory pathway; trafficking.

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Figures

FIGURE 1
FIGURE 1
ERp29 structure. (A) The structural alignment of ERp29 protein functional domains from human, mouse, and Drosophila melanogaster. (B) Cartoon of the proposed ERp29 complex at the ER membrane (partially created with BioRender.com). The color scheme between (A,B) is consistent, demonstrating ERp29 dimerization at the N-terminus domain interface and serving as a linker of a larger protein complex.
FIGURE 2
FIGURE 2
ERp29 in protein trafficking. Schematic representation of ERp29 role in ER to Golgi secretory pathway (image created with BioRender.com).
FIGURE 3
FIGURE 3
ERp29 role in the unfolded protein response (UPR). Schematic representation of UPR pathways, highlighting the potential site of ERp29 action (image created with BioRender.com).
See this image and copyright information in PMC

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