title: The GTPase Rab37 Participates in the Control of Insulin Exocytosis.
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.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors.forename: Sanda
authors.initials: S
authors.lastname: Ljubicic
authors.forename: Paola
authors.initials: P
authors.lastname: Bezzi
authors.forename: Saska
authors.initials: S
authors.lastname: Brajkovic
authors.forename: Valeria
authors.initials: V
authors.lastname: Nesca
authors.forename: Claudiane
authors.initials: C
authors.lastname: Guay
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ohbayashi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Amar
authors.initials: A
authors.lastname: Abderrhamani
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
mesh_terms: D002460:Cell Line; D005089:Exocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; C485184:enhanced green fluorescent protein; D000075745:rab27 GTP-Binding Proteins; D019382:Human Growth Hormone; D049452:Green Fluorescent Proteins; C571080:Rab37 protein, human; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein; D005947:Glucose