ArticleProceedings of the National Academy of Sciences of the United States of America2004
Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 81 citations in OpenAlex.
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- Novel insights regarding the role of noncoding RNAs in diabetes.World journal of diabetes · 2023Review
- Whole-genome resequencing reveals domestication and signatures of selection in Ujimqin, Sunit, and Wu Ranke Mongolian sheep breeds.Animal bioscience · 2022Article
- In vivo Roles of Rab27 and Its Effectors in Exocytosis.Cell structure and function · 2021Review
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.Genome medicine · 2021Article
- Differential expression profiles of microRNAs in musk gland of unmated and mated forest musk deer (PeerJ · 2021Article
- Molecular Regulatory Mechanism of Exocytosis in the Salivary Glands.International journal of molecular sciences · 2018Review
- Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature.eLife · 2018Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Micromanaging Glucose Tolerance and Diabetes.Advanced pharmaceutical bulletin · 2017Review
- Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration.Journal of virology · 2017Article
- The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells.Nature communications · 2016Article
- Interplay between Rab27a effectors in pancreatic β-cells.World journal of diabetes · 2015Review
- Article
- Activated Cdc42-bound IQGAP1 determines the cellular endocytic site.Molecular and cellular biology · 2013Article
- Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors.Journal of leukocyte biology · 2013Review
- The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane.Molecular biology of the cell · 2013Article
- Article
- A novel function of Noc2 in agonist-induced intracellular Ca2+ increase during zymogen-granule exocytosis in pancreatic acinar cells.PloS one · 2012Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors of Rab3, including rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2 was identified originally in endocrine pancreas as a molecule homologous to rabphilin3, but its role in exocytosis is unclear. To clarify the physiological function of Noc2 directly, we have generated Noc2 knockout (Noc2(-/-)) mice. Glucose intolerance with impaired insulin secretion was induced in vivo by acute stress in Noc2(-/-) mice, but not in wild-type (Noc2(+/+)) mice. Ca(2+)-triggered insulin secretion from pancreatic isles of Noc2(-/-) mice was markedly impaired, but was completely restored by treatment with pertussis toxin, which inhibits inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of clonidine, an alpha(2)-adrenoreceptor agonist, on insulin secretion was significantly greater in Noc2(-/-) islets than in Noc2(+/+) islets. Impaired Ca(2+)-triggered insulin secretion was rescued by adenovirus gene transfer of wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3. Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required for the effect. Interestingly, we also found a marked accumulation of secretory granules in various exocrine cells of Noc2(-/-) mice, especially in exocrine pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells.
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