RGD Reference Report - Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP. - Rat Genome Database

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Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP.

Authors: Hussain, Syed Saad  Harris, Megan T  Kreutzberger, Alex J B  Inouye, Candice M  Doyle, Catherine A  Castle, Anna M  Arvan, Peter  Castle, J David 
Citation: Hussain SS, etal., Mol Biol Cell. 2018 May 15;29(10):1238-1257. doi: 10.1091/mbc.E17-08-0519. Epub 2018 Mar 22.
RGD ID: 41404656
Pubmed: (View Article at PubMed) PMID:29540530
DOI: Full-text: DOI:10.1091/mbc.E17-08-0519

In pancreatic β-cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood. ATP binding cassette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi inter-ference-induced depletion in cultured pancreatic β-cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent. Both transporters are also required for optimum glucose-stimulated insulin secretion, likely via complementary roles. Exogenous cholesterol addition rescues knockdown-induced granule loss (ABCG1) and reduced secretion (both transporters). Another cholesterol transport protein, oxysterol binding protein (OSBP), appears to act proximally as a source of endogenous cholesterol for granule formation. Its knockdown caused similar defective stability of young granules and glucose-stimulated insulin secretion, neither of which were rescued with exogenous cholesterol. Dual knockdowns of OSBP and ABC transporters support their serial function in supplying and concentrating cholesterol for granule formation. OSBP knockdown also decreased proinsulin synthesis consistent with a proximal endoplasmic reticulum defect. Thus, membrane cholesterol distribution contributes to insulin homeostasis at production, packaging, and export levels through the actions of OSBP and ABCs G1 and A1.

Annotation

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Abcg1  (ATP binding cassette subfamily G member 1)
Osbp  (oxysterol binding protein)


Additional Information