Rim2α Determines Docking and Priming States in Insulin Granule Exocytosis
Open accessAbstract
Insulin secretion is essential for maintenance of glucose homeostasis, but the mechanism of insulin granule exocytosis, the final step of insulin secretion, is largely unknown. Here, we investigated the role of Rim2alpha in insulin granule exocytosis, including the docking, priming, and fusion steps. We found that interaction of Rim2alpha and Rab3A is required for docking, which is considered a brake on fusion events, and that docking is necessary for K(+)-induced exocytosis, but not for glucose-induced exocytosis. Furthermore, we found that dissociation of the Rim2alpha/Munc13-1 complex by glucose stimulation activates Syntaxin1 by Munc13-1, indicating that Rim2alpha primes insulin granules for fusion. Thus, Rim2alpha determines docking and priming states in insulin granule exocytosis depending on its interacting partner, Rab3A or Munc13-1, respectively. Because Rim2alpha(-/-) mice exhibit impaired secretion of various hormones stored as dense-core granules, including glucose-dependent insulinotropic polypeptide, growth hormone, and epinephrine, Rim2alpha plays a critical role in exocytosis of these dense-core granules.
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Ablation of Rims2 leads to impaired glucose tolerance and inhibition of GIIS or high K+-induced insulin secretion.
“Ablation of Rims2 leads to impaired glucose tolerance and inhibition GIIS or high K+-induced insulin secretion (750).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [750]
The Introduction (p. 5) says Rim2α is required for insulin-granule exocytosis and that docking is necessary for K+-induced exocytosis, supporting a role in stimulated insulin release. The retrieved passages do not report impaired glucose tolerance or directly state that Rim2α ablation inhibits glucose- or high-K+-induced insulin secretion. (LLM, conf=0.68)
Experimental — accuracy not yet measuredRim2 interacts with Rab3A and Munc13-1, and also interacts with the cAMP-sensing protein cAMP-GEFII/Epac2.
“Like Rim1, Rim2 interacts with Rab3A (496) and Munc13-1 (160, 750). It also interacts with the cAMP-sensing protein cAMP-GEFII (also known as Epac2) (496, 615).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [750]
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Research works printed but not linked: 2
- Matsumoto, M., Miki, T., Shibasaki, T., Kawaguchi, M., Shinozaki, H., Nio, J., Saraya, A., Koseki, H., Miyazaki, M., Iwanaga, T., and Seino, S. (2004). Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells. Proc. Natl. Acad. Sci. USA 101 , 8313-8318.
- Shibasaki, T., Takahashi, H., Miki, T., Sunaga, Y., Matsumura, K., Yamanaka, M., Zhang, C., Tamamoto, A., Satoh, T., Miyazaki, J., and Seino, S. (2007). Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc. Natl. Acad. Sci. USA 104 , 19333-19338.
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- Authors
- Yasuda, T., Shibasaki, T., Minami, K., Takahashi, H., Mizoguchi, A., Uriu, Y., Numata, T., Mori, Y., Miyazaki, J.-I., Miki, T., & Seino, S.
- Affiliations
- Kobe University (JP)
- Mie University (JP)
- Kyoto University (JP)
- The University of Osaka (JP)
- Chiba University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Seino, Susumu
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 12
- Issue
- 2
- Pages
- 117-129
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2068443011
- Cited by
- 110
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 10 · 2022: 5 · 2021: 11 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 4 · 2015: 9 · 2014: 6 · 2013: 4 · 2012: 17
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kobe University Repository Kernel (Kobe University) (submittedVersion, other-oa)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- insulin secretion, insulin granule exocytosis, Rab3A, Munc13-1, docking, dense core granules, glucose-dependent insulinotropic polypeptide, growth hormone, epinephrine
- MeSH terms
- Insulin Secretion, Animals, Exocytosis, Insulin, Nerve Tissue Proteins, Potassium, GTP-Binding Proteins, rab3 GTP-Binding Proteins, rab3A GTP-Binding Protein, Secretory Vesicles, Insulin-Secreting Cells, Syntaxin 1, Mice
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