Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation

Bisnett, Brittany; Condon, Brett M; Linhart, Noah A; Lamb, Caitlin H.; Huynh, Duc T.; Bai, Jian; Smith, Timothy J.; Hu, Jimin; Georgiou, George R.; Boyce, Michael

doi:10.1101/2020.12.30.424839

Cited by 5 publications

(5 citation statements)

References 131 publications

(232 reference statements)

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“…Multiple single-cell derived knockout clones per each guide RNA were isolated and screened for the gene disruption by western blotting. SEC24C and SEC24D KO cell lines were described previously (Bisnett et al , 2021). Cells were validated by immunoblotting or quantitative RT-PCR (Figure S8).…”

Section: Methodsmentioning

confidence: 99%

Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export

Gómez-Navarro

Maldutyte

Poljak

et al. 2022

Preprint

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Protein secretion is an essential cellular process that permits cell growth, movement and communication. Traffic of proteins within the eukaryotic secretory pathway is mediated by transport intermediates that bud from one compartment, populated with appropriate cargo proteins, and fuse with a downstream compartment to deliver their contents. Here, we explore the possibility that protein secretion can be selectively inhibited by perturbing protein-protein interactions that drive capture into transport vesicles. Human PCSK9 is a major determinant of cholesterol metabolism, whose secretion is mediated by a specific cargo adaptor of the ER export machinery, SEC24A. We map a series of protein-protein interactions between PCSK9, its ER export receptor, SURF4, and SEC24A, that mediate secretion of PCSK9. We show that the interaction between SURF4 and SEC24A can be inhibited by 4-PBA, a small molecule that occludes a cargo-binding domain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4 clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected. We propose that selective small molecule inhibition of cargo recognition by SEC24 is a potential therapeutic intervention for atherosclerosis and other diseases that are modulated by secreted proteins.

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Section: Methodsmentioning

confidence: 99%

Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export

Gómez-Navarro

Maldutyte

Poljak

et al. 2022

Preprint

Self Cite

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“…The anterograde and retrograde trafficking pathways need to be balanced within the cell and are highly dynamic. In order to efficiently balance and interlink cellular processes, posttranslational modifications (PTMs) of all ERES component proteins and some cargo receptors have been reported (Bisnett et al, 2020). These modifications demonstrate the complexity of regulation of the early secretory pathway: the need for fast regulation of ER exit, and the need for repurposing ERES for non-canonical roles, that we have recently started to understand.…”

Section: Eres Regulationmentioning

confidence: 99%

ER exit in physiology and disease

Robinson,

Duggan,

Forrester

2024

Front. Mol. Biosci.

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The biosynthetic secretory pathway is comprised of multiple steps, modifications and interactions that form a highly precise pathway of protein trafficking and secretion, that is essential for eukaryotic life. The general outline of this pathway is understood, however the specific mechanisms are still unclear. In the last 15 years there have been vast advancements in technology that enable us to advance our understanding of this complex and subtle pathway. Therefore, based on the strong foundation of work performed over the last 40 years, we can now build another level of understanding, using the new technologies available. The biosynthetic secretory pathway is a high precision process, that involves a number of tightly regulated steps: Protein folding and quality control, cargo selection for Endoplasmic Reticulum (ER) exit, Golgi trafficking, sorting and secretion. When deregulated it causes severe diseases that here we categorise into three main groups of aberrant secretion: decreased, excess and altered secretion. Each of these categories disrupts organ homeostasis differently, effecting extracellular matrix composition, changing signalling events, or damaging the secretory cells due to aberrant intracellular accumulation of secretory proteins. Diseases of aberrant secretion are very common, but despite this, there are few effective therapies. Here we describe ER exit sites (ERES) as key hubs for regulation of the secretory pathway, protein quality control and an integratory hub for signalling within the cell. This review also describes the challenges that will be faced in developing effective therapies, due to the specificity required of potential drug candidates and the crucial need to respect the fine equilibrium of the pathway. The development of novel tools is moving forward, and we can also use these tools to build our understanding of the acute regulation of ERES and protein trafficking. Here we review ERES regulation in context as a therapeutic strategy.

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“…SEC24 is the cargo binding protein (Miller et al, 2002) interacting with several different ER export motifs through various domains (Miller et al, 2003). The SEC23/ SEC24 heterodimer also provides the platform for the recruitment of the outer layer of the COPII coat, a heterodimer formed by SEC13 and SEC31 (Sato and Nakano, 2007;Bisnett et al, 2020).…”

Section: The Early Conventional Secretory Pathway Between Er and Golg...mentioning

confidence: 99%

Impact of interorganelle coordination between the conventional early secretory pathway and autophagy in cellular homeostasis and stress response

Tapia

Cavieres

Burgos

et al. 2023

Front. Cell Dev. Biol.

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The conventional early secretory pathway and autophagy are two essential interconnected cellular processes that are crucial for maintaining cellular homeostasis. The conventional secretory pathway is an anabolic cellular process synthesizing and delivering proteins to distinct locations, including different organelles, the plasma membrane, and the extracellular media. On the other hand, autophagy is a catabolic cellular process that engulfs damaged organelles and aberrant cytosolic constituents into the double autophagosome membrane. After fusion with the lysosome and autolysosome formation, this process triggers digestion and recycling. A growing list of evidence indicates that these anabolic and catabolic processes are mutually regulated. While knowledge about the molecular actors involved in the coordination and functional cooperation between these two processes has increased over time, the mechanisms are still poorly understood. This review article summarized and discussed the most relevant evidence about the key molecular players implicated in the interorganelle crosstalk between the early secretory pathway and autophagy under normal and stressful conditions.

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Evidence for nutrient-dependent regulation of the COPII coat by O-GlcNAcylation

Cited by 5 publications

References 131 publications

Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export

Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export

ER exit in physiology and disease

Impact of interorganelle coordination between the conventional early secretory pathway and autophagy in cellular homeostasis and stress response

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