ArticleScientific reports2014
Rab2A is a pivotal switch protein that promotes either secretion or ER-associated degradation of (pro)insulin in insulin-secreting cells.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
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- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Potential molecular mechanism of ACE gene at different time points in STEMI patients based on genome-wide microarray dataset.Lipids in health and disease · 2019Article
- Biosynthesis, structure, and folding of the insulin precursor protein.Diabetes, obesity & metabolism · 2018Review
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- Establishment and phenotyping of disease model cells created by cell-resealing technique.Scientific reports · 2017Article
- A TRPV1-to-secretagogin regulatory axis controls pancreatic β-cell survival by modulating protein turnover.The EMBO journal · 2017Article
- The impact of erdosteine on cisplatin-induced ototoxicity: a proteomics approach.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2017Article
- Rab1A mediates proinsulin to insulin conversion in β-cells by maintaining Golgi stability through interactions with golgin-84.Protein & cell · 2016Article
- RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs.EMBO reports · 2016Article
- Spatial and Functional Aspects of ER-Golgi Rabs and Tethers.Frontiers in cell and developmental biology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rab2A, a small GTPase localizing to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), regulates COPI-dependent vesicular transport from the ERGIC. Rab2A knockdown inhibited glucose-stimulated insulin secretion and concomitantly enlarged the ERGIC in insulin-secreting cells. Large aggregates of polyubiquitinated proinsulin accumulated in the cytoplasmic vicinity of a unique large spheroidal ERGIC, designated the LUb-ERGIC. Well-known components of ER-associated degradation (ERAD) also accumulated at the LUb-ERGIC, creating a suitable site for ERAD-mediated protein quality control. Moreover, chronically high glucose levels, which induced the enlargement of the LUb-ERGIC and ubiquitinated protein aggregates, impaired Rab2A activity by promoting dissociation from its effector, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in response to poly (ADP-ribosyl)ation of GAPDH. The inactivation of Rab2A relieved glucose-induced ER stress and inhibited ER stress-induced apoptosis. Collectively, these results suggest that Rab2A is a pivotal switch that controls whether insulin should be secreted or degraded at the LUb-ERGIC and Rab2A inactivation ensures alleviation of ER stress and cell survival under chronic glucotoxicity.
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