Cited by 53Cellular transport and secretionPancreatic function and diabetesProtein Kinase Regulation and GTPase Signaling

ICA69 is a novel Rab2 effector regulating ER-Golgi trafficking in insulinoma cells

Buffa, Laura, Fuchs, Evelyn, Pietropaolo, Massimo, Barr, Francis, Solimena, Michele·2008·European Journal of Cell Biology

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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Crossref · 10.1016/j.ejcb.2007.11.003

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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
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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