ICA69 is a novel Rab2 effector regulating ER-Golgi trafficking in insulinoma cells
Abstract
Islet cell autoantigen of 69kDa (ICA69) is a small GTPase-binding protein of unknown function. ICA69 is enriched in the Golgi complex and its N-terminal half contains a BAR domain, a module that can bind/bend membranes and interacts with phospholipids. Here we show that in insulinoma INS-1 cells ICA69 binds to the small GTPase Rab2, which regulates the transport of COPI vesicles between the endoplasmic reticulum and the Golgi complex. Rab2 binds to ICA69 in a GTP-dependent fashion and recruits it to membranes. Over-expression of either Rab2 or ICA69 in INS-1 cells results in a phenotype characterized by: (i) impaired anterograde transport of the secretory granule protein precursors pro-ICA512 and chromogranin A; (ii) reduction of stimulated insulin secretion. Taken together, these data identify ICA69 as a novel Rab2 effector and point to its role in regulating the early transport of insulin secretory granule proteins.
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Rab2a is a Golgi-resident GTPase governing intra-Golgi trafficking.
“Rab2a is known to be a Golgi-resident GTPase, governing intra-Golgi trafficking (Buffa et al., 2008; Ailion et al., 2014).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Buffa et al., 2008
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- Authors
- Buffa, L., Fuchs, E., Pietropaolo, M., Barr, F., & Solimena, M.
- Affiliations
- Technische Universität Dresden (DE)
- University of Liverpool (GB)
- University of Michigan (US)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Corresponding author
- Solimena, Michele
- Venue
- European Journal of Cell Biology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 87
- Issue
- 4
- Pages
- 197-209
- ISSN
- 0171-9335 (ISSN-L)
- OpenAlex
- W2055367681
- Cited by
- 53
- References
- 52
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- European Journal of Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Site cant be reached (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Ludwig Institute for Cancer Research
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- 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 › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Rab2, Rab GTPase effectors, ER-Golgi trafficking, COPI vesicles, BAR domain, Golgi apparatus, insulinoma, INS-1 cells, chromogranin A, insulin secretion
- MeSH terms
- Insulin Secretion, Autoantigens, Binding Sites, Endoplasmic Reticulum, Golgi Apparatus, Humans, Insulin, Insulinoma, Pancreatic Neoplasms, Protein Binding, rab2 GTP-Binding Protein, Coatomer Protein, Protein Transport, Secretory Vesicles, Cell Line, Tumor, Chromogranin A, Receptor-Like Protein Tyrosine Phosphatases, Class 8
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