A general role for MIA3/TANGO1 in secretory pathway organization and function

McCaughey, Janine; Mantell, Judith; Neal, Chris; Heesom, Kate J; Stephens, David

doi:10.1101/2021.02.24.432632

Cited by 2 publications

(2 citation statements)

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“…TANGO1's facilitating role in formation of large COPII vesicles is unequivocal (McCaughey et al, 2021a;Saito et al, 2009), yet there are reports of its ambiguous mechanism in the generation of large COPII vesicles. Schekman and colleagues suggest a co-packaging of TANGO1 with the cargo (Yuan et al, 2018), whereas Malhotra and colleagues demonstrated that TANGO1 does not leave the ER, but forms a ring around the COPII vesicle (Raote et al, 2018).…”

Section: Trafficking Of Mucin-2 In Enlarged Copii Vesicles Is Reminis...mentioning

confidence: 99%

“…Overexpressing TANGO and KLHL12 confirmed their promoting role for mucin-2 trafficking as has been observed for PC1 (28), collagen IV (74) and apoB (73) trafficking, through the mono-ubiquitylation of SEC31. TANGO1's facilitating role in formation of large COPII vesicles is unequivocal (31,75), yet there are reports of its ambiguous mechanism in the generation of large COPII vesicles. Schekman and colleagues suggest a co-packaging of TANGO1 with the cargo (29), whereas Malhotra and colleagues demonstrated that TANGO1 does not leave the ER, but forms a ring around the COPII vesicle (33).…”

Section: Trafficking Of Mucin-2 In Enlarged Copii Vesicles Is Reminis...mentioning

confidence: 99%

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Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Morsink,

Koch,

et al. 2024

Preprint

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The intestinal mucous layer relies on mucin-2 secretion. While the mucin-2 secretory pathway has been studied, endoplasmic reticulum (ER) to Golgi apparatus (Golgi) trafficking remains poorly understood. The size of mucin-2 exceeds the capacity of regular coat protein complex II (COPII) vesicles, responsible for ER-to-Golgi transport. After confirming conventional secretion of mucin-2, we showed that COPII vesicle enlargement is facilitated by TANGO1 and cTAGE5, and promoted by KLHL12. Inflammatory bowel disease (IBD) is characterized by a compromised mucous layer, altered activity of Transforming Growth Factor beta (TGF-beta), and increased ER stress. Using a cell culture, we showed that TGF-beta inhibition induces TANGO1-mediated ER stress. Mucosal gene expression analysis in IBD patients confirmed elevated ER stress and validated concomitantly altered mRNA levels of TGF-beta with mucin-2 and transport proteins TANGO1 and cTAGE5. In conclusion, we propose that the unsuccessful formation of enlarged COPII vesicles could be a source of ER stress in IBD, because of lowered TANGO1 protein expression, subsequently leading to decreased mucin-2 secretion.

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Section: Trafficking Of Mucin-2 In Enlarged Copii Vesicles Is Reminis...mentioning

confidence: 99%

Section: Trafficking Of Mucin-2 In Enlarged Copii Vesicles Is Reminis...mentioning

confidence: 99%

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Morsink,

Koch,

et al. 2024

Preprint

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Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum

Cain

Brudvig

et al. 2021

Preprint

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Procollagen requires COPII coat proteins for export from the endoplasmic reticulum (ER). SEC24 is the major component of the COPII proteins that selects cargo during COPII vesicle assembly. There are four paralogs (A to D) of SEC24 in mammals, which are classified into two subgroups. Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans and sec24d mutant fish also recapitulating these phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient-derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. To explore this possibility, we generated Sec24d knockout (KO) mice. Homozygous KO mice died prior to bone development. When we analyzed embryonic and extraembryonic tissues of mutant animals, we observed tissue-dependent defects of procollagen processing and ER export. The spacial patterns of these defects mirrored with SEC24B deficiency. By systematically knocking down the expression of Sec24 paralogs, we revealed that, in addition to SEC24C and SEC24D, SEC24A and SEC24B also contribute to collagen secretion. In contrast, fibronectin 1 preferred either SEC24C or SEC24D. Taken together, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.

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A general role for MIA3/TANGO1 in secretory pathway organization and function

Cited by 2 publications

References 73 publications

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Fundamental transport mechanism of mucin-2 ER-to-Golgi trafficking identifies source of ER stress in inflammatory bowel disease

Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum

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