The GTPase Rab37 Participates in the Control of Insulin Exocytosis

Sanda Ljubicic, Paola Bezzi, Saska Brajkovic, Valeria Nesca, Claudiane Guay, Norihiko Ohbayashi, Mitsunori Fukuda, Amar Abderrhamani, Romano Regazzi

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    Rab37 belongs to a subclass of Rab GTPases regulating exocytosis, including also Rab3a and Rab27a. Proteomic studies indicate that Rab37 is associated with insulin-containing large dense core granules of pancreatic β-cells. In agreement with these observations, we detected Rab37 in extracts of β-cell lines and human pancreatic islets and confirmed by confocal microscopy the localization of the GTPase on insulin-containing secretory granules. We found that, as is the case for Rab3a and Rab27a, reduction of Rab37 levels by RNA interference leads to impairment in glucose-induced insulin secretion and to a decrease in the number of granules in close apposition to the plasma membrane. Pull-down experiments revealed that, despite similar functional effects, Rab37 does not interact with known Rab3a or Rab27a effectors and is likely to operate through a different mechanism. Exposure of insulin-secreting cells to proinflammatory cytokines, fatty acids or oxidized low-density lipoproteins, mimicking physiopathological conditions that favor the development of diabetes, resulted in a decrease in Rab37 expression. Our data identify Rab37 as an additional component of the machinery governing exocytosis of β-cells and suggest that impaired expression of this GTPase may contribute to defective insulin release in pre-diabetic and diabetic conditions.

    Original languageEnglish
    Article numbere68255
    JournalPloS one
    Volume8
    Issue number6
    DOIs
    Publication statusPublished - 2013 Jun 27

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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