Protein quality control at the Golgi

Schwabl, Sinead; Teis, David

doi:10.1016/j.ceb.2022.02.008

Cited by 16 publications

(16 citation statements)

References 80 publications

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“…Apart from vacuolar degradation, some proteins also undergo proteasomal degradation by “endosome and Golgi associated degradation (EGAD)”. However, the mechanism of substrate recognition and the decision of ER retrieval vs degradation remains unclear ( Rosquete et al, 2018 ; Hellerschmied et al, 2019 ; Benyair et al, 2022 ; Schwabl and Teis, 2022 ). Although likely, the involvement of an Hsp70:JDP in this process is not reported as yet.…”

Section: Protein Quality Control In Golgimentioning

confidence: 99%

“…At each of these steps, PM proteins must pass the “fit to move forward” test. In case they do not meet the quality control (QC) standards, they are appropriately handled by one or the other component(s) of the cellular PQC machinery ( Anelli and Sitia, 2008 ; Okiyoneda et al, 2011 ; Sun and Brodsky, 2019 ; Phillips et al, 2020 ; Schwabl and Teis, 2022 ). At the PM, too, these proteins are constantly at risk of misfolding or aggregation.…”

Section: Introductionmentioning

confidence: 99%

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Volleying plasma membrane proteins from birth to death: Role of J-domain proteins

Sagarika

Yadav

Sahi

2022

Front. Mol. Biosci.

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The function, stability, and turnover of plasma membrane (PM) proteins are crucial for cellular homeostasis. Compared to soluble proteins, quality control of plasma membrane proteins is extremely challenging. Failure to meet the high quality control standards is detrimental to cellular and organismal health. J-domain proteins (JDPs) are among the most diverse group of chaperones that collaborate with other chaperones and protein degradation machinery to oversee cellular protein quality control (PQC). Although fragmented, the available literature from different models, including yeast, mammals, and plants, suggests that JDPs assist PM proteins with their synthesis, folding, and trafficking to their destination as well as their degradation, either through endocytic or proteasomal degradation pathways. Moreover, some JDPs interact directly with the membrane to regulate the stability and/or functionality of proteins at the PM. The deconvoluted picture emerging is that PM proteins are relayed from one JDP to another throughout their life cycle, further underscoring the versatility of the Hsp70:JDP machinery in the cell.

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Section: Protein Quality Control In Golgimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Volleying plasma membrane proteins from birth to death: Role of J-domain proteins

Sagarika

Yadav

Sahi

2022

Front. Mol. Biosci.

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“…Despite the pivotal role of the Golgi in protein sorting, and in cellularand organismal health, Golgi-based protein quality control (PQC) processes have remained largely unknown. While there is emerging evidence that PQC systems operate at the Golgi [4][5][6][7] to detect and degrade misfolded and orphaned proteins (proteins that mislocalize or fail to assemble with their protein binding partners 8,9 ), the underlying molecular mechanisms are not well characterized [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi

Weyer,

Schwabl,

Tang

et al. 2024

Preprint

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The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex, particularly the rhomboid pseudo-protease subunit, Dsc2, assesses the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be K63 polyubiquitinated for ESCRT dependent vacuolar degradation or K48 polyubiquitinated for endosome and Golgi associated proteasomal degradation (EGAD). Other Dsc substrates are exclusively extracted by Cdc48 for EGAD. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thus preserves cellular membrane protein and lipid composition.

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“…Recent studies indicate that the Golgi functions as a signaling hub in intracellular signal transduction pathways involved in the development and progression of many diseases ( Cancino and Luini, 2013 ; Makhoul et al, 2019 ; Spano and Colanzi, 2022 ). The pathophysiological involvement of the Golgi is attracting interest because protein quality control, which is known to have a significant association with the pathogenesis of numerous diseases, is associated with the Golgi ( Schwabl and Teis, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

Kim

Choi

Deshar

et al. 2023

Molecules and Cells

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The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

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Protein quality control at the Golgi

Cited by 16 publications

References 80 publications

Volleying plasma membrane proteins from birth to death: Role of J-domain proteins

Volleying plasma membrane proteins from birth to death: Role of J-domain proteins

The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

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