cAMP-GEFII is a direct target of cAMP in regulated exocytosis
Abstract
Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.
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Rim2 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 [496]
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References 43 · Cited by 481
- Authors
- Ozaki, N., Shibasaki, T., Kashima, Y., Miki, T., Takahashi, K., Ueno, H., Sunaga, Y., Yano, H., Matsuura, Y., Iwanaga, T., Takai, Y., & Seino, S.
- Affiliations
- Chiba University (JP)
- National Institute of Infectious Diseases (JP)
- Hokkaido University (JP)
- The University of Osaka (JP)
- Corresponding author
- Seino, Susumu
- Venue
- Nature Cell Biology
- Published
- 2000-10-10
- Volume
- 2
- Issue
- 11
- Pages
- 805-811
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2171483278
- Cited by
- 481
- References
- 43
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 14 · 2018: 9 · 2017: 13 · 2016: 8 · 2015: 12 · 2014: 25 · 2013: 29 · 2012: 29
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk Pharma
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- cAMP signaling, regulated exocytosis, RIM, Rab3, vesicle fusion, protein kinase A, secretory cells, protein-protein interaction
- MeSH terms
- Cyclic AMP, Animals, Base Sequence, Carrier Proteins, Cyclic AMP Receptor Protein, Chlorocebus aethiops, Exocytosis, Molecular Sequence Data, Nerve Tissue Proteins, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, GTP-Binding Proteins, COS Cells, Mice, Rats
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