The KDEL receptor has a role in the biogenesis and trafficking of the epithelial sodium channel (ENaC)

Bikard, Yann; Viviano, Jeffrey; Orr, Melissa N.; Brown, Lauren; Brecker, Margaret; Jeger, Jonathan Litvak; Grits, Daniel; Suaud, Laurence; Rubenstein, Ronald C.

doi:10.1074/jbc.ra119.008331

Cited by 10 publications

(20 citation statements)

References 37 publications

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“…Furthermore, we demonstrated that deletion of ERp29's C-terminal -K-E-E-L ER retention motif (a KDEL homolog) reduced the interaction of ENaC with the Sec24D as seen in co-immunoprecipitation experiments (CFBE41o-and MDCK cells). Similar effects on ENaC biogenesis were observed with depletion of KDEL-R1 or Sec24D (Bikard et al, 2019). Taken together, these data suggest ERp29, through an interaction with KDEL-R1, regulates ENaC biogenesis, which indicates a novel role for KDEL-R1 in anterograde protein trafficking.…”

Section: Shuttling Of Erp29 Between the Er And Golgisupporting

confidence: 71%

“…Similarly, we demonstrated that depletion of Sec24D protein expression reduces the number of cleaved subunits on the cell surface but does not reduce the amount of β-ENaC at the cell surface. These data suggest that when the COP II ER exit pathway is blocked, ENaC can still reach the plasma membrane by a non-COP II pathway that allows the channel to bypass cleavage by furin in the Golgi or later compartments (Bikard et al, 2019).…”

Section: Epithelial Sodium Channel (Enac)mentioning

confidence: 87%

“…With regards to the KDEL-R having a role in anterograde ER→Golgi trafficking via COP II, our group has recently found that ERp29 likely interacts with KDEL-R1 as part of the anterograde trafficking of the epithelial sodium channel (ENaC) in CFBE41o-CF bronchial epithelial cells and MDCK renal epithelial cells (Bikard et al, 2019). Furthermore, we demonstrated that deletion of ERp29's C-terminal -K-E-E-L ER retention motif (a KDEL homolog) reduced the interaction of ENaC with the Sec24D as seen in co-immunoprecipitation experiments (CFBE41o-and MDCK cells).…”

Section: Shuttling Of Erp29 Between the Er And Golgimentioning

confidence: 99%

“…The current understanding of the KDEL-R role in the secretory protein pathway is limited to its role in vesicle transport by COP I. However, there are recent reports that observed KDEL-R at the plasma membrane of the cell (Becker et al, 2016), as well as data supporting the hypothesis that KDEL-R has a role in COP II-mediated ER→Golgi trafficking (Bikard et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…ERp29 is ubiquitously expressed throughout the different tissue types (Shnyder and Hubbard, 2002), especially in secretory tissues, and is implicated in the biogenesis of many proteins ( Table 1). Our group's work has demonstrated that ERp29 promotes CFTR maturation (Suaud et al, 2011a) and regulates the maturation of the epithelial sodium channel (ENaC) (Grumbach et al, 2014;Bikard et al, 2019) in epithelial cells. In addition, our group's recent data have suggested a role for ERp29 in regulating proinsulin biosynthesis (Viviano et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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The Probable, Possible, and Novel Functions of ERp29

et al. 2020

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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.

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Section: Shuttling Of Erp29 Between the Er And Golgisupporting

confidence: 71%

Section: Epithelial Sodium Channel (Enac)mentioning

confidence: 87%

Section: Shuttling Of Erp29 Between the Er And Golgimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Probable, Possible, and Novel Functions of ERp29

et al. 2020

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“Sticki-ER”: Functions of the Platelet Endoplasmic Reticulum

Kong,

Chiu,

Passam

2024

Antioxidants & Redox Signaling

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A systematic review of Sec24 cargo interactome

Chatterjee

Choi

Frankel

2021

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Endoplasmic reticulum (ER)‐to‐Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex‐II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one‐third of all mammalian proteins rely on the COPII‐mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog‐specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. We also discuss how the Sec24 secretion system is hijacked by viral (eg, VSV‐G, Hepatitis B envelope protein) and bacterial (eg, the enteropathogenic Escherichia coli type III secretion system effector NleA/EspI) pathogens.

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The KDEL receptor has a role in the biogenesis and trafficking of the epithelial sodium channel (ENaC)

Cited by 10 publications

References 37 publications

The Probable, Possible, and Novel Functions of ERp29

The Probable, Possible, and Novel Functions of ERp29

“Sticki-ER”: Functions of the Platelet Endoplasmic Reticulum

A systematic review of Sec24 cargo interactome

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