Translation of insulin granule proteins are regulated by PDI and PABP

Sarwade, Rucha D.; Khalique, Abdul; Kulkarni, Shardul D.; Pandey, Poonam R; Gaikwad, Naina; Seshadri, Vasudevan

doi:10.1016/j.bbrc.2020.03.106

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…ERp57 has been previously shown to regulate the steady-state levels of wild-type and mutant prion protein (PrP), up to 50% (Torres et al, 2015 ), implying that it can modulate the expression of proteins closely associated with neurodegeneration. Similarly, PDI is also known to regulate the translation of insulin granule proteins by binding to 5’ UTR sequences within their mRNA (Sarwade et al, 2020 ). TDP-43 regulates its own expression levels by a negative feedback loop in which it targets a sequence in the 3′ UTR of its own transcript (Ayala et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells

Parakh,

Perri,

Vidal

et al. 2024

Neuromol Med

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Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting motor neurons. Pathological forms of Tar-DNA binding protein-43 (TDP-43), involving its mislocalisation to the cytoplasm and the formation of misfolded inclusions, are present in almost all ALS cases (97%), and ~ 50% cases of the related condition, frontotemporal dementia (FTD), highlighting its importance in neurodegeneration. Previous studies have shown that endoplasmic reticulum protein 57 (ERp57), a member of the protein disulphide isomerase (PDI) family of redox chaperones, is protective against ALS-linked mutant superoxide dismutase (SOD1) in neuronal cells and transgenic SOD1G93A mouse models. However, it remains unclear whether ERp57 is protective against pathological TDP-43 in ALS. Here, we demonstrate that ERp57 is protective against key features of TDP-43 pathology in neuronal cells. ERp57 inhibited the mislocalisation of TDP-43M337V from the nucleus to the cytoplasm. In addition, ERp57 inhibited the number of inclusions formed by ALS-associated variant TDP-43M337V and reduced the size of these inclusions. ERp57 was also protective against ER stress and induction of apoptosis. Furthermore, ERp57 modulated the steady-state expression levels of TDP-43. This study therefore demonstrates a novel mechanism of action of ERp57 in ALS. It also implies that ERp57 may have potential as a novel therapeutic target to prevent the TDP-43 pathology associated with neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells

Parakh,

Perri,

Vidal

et al. 2024

Neuromol Med

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mRNA Processing: An Emerging Frontier in the Regulation of Pancreatic β Cell Function

Moss

Sussel

2020

Front. Genet.

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Robust endocrine cell function, particularly β cell function, is required to maintain blood glucose homeostasis. Diabetes can result from the loss or dysfunction of β cells. Despite decades of clinical and basic research, the precise regulation of β cell function and pathogenesis in diabetes remains incompletely understood. In this review, we highlight RNA processing of mRNAs as a rapidly emerging mechanism regulating β cell function and survival. RNA-binding proteins (RBPs) and RNA modifications are primed to be the next frontier to explain many of the poorly understood molecular processes that regulate β cell formation and function, and provide an exciting potential for the development of novel therapeutics. Here we outline the current understanding of β cell specific functions of several characterized RBPs, alternative splicing events, and transcriptome wide changes in RNA methylation. We also highlight several RBPs that are dysregulated in both Type 1 and Type 2 diabetes, and discuss remaining knowledge gaps in the field.

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Translation of insulin granule proteins are regulated by PDI and PABP

Cited by 2 publications

References 33 publications

Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells

Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells

mRNA Processing: An Emerging Frontier in the Regulation of Pancreatic β Cell Function

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