The GTPase Rab37 Participates in the Control of Insulin Exocytosis.
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-cel...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3694898?pdf=render |
id |
doaj-00cbb79d31874e1283bd2989ec4ec076 |
---|---|
record_format |
Article |
spelling |
doaj-00cbb79d31874e1283bd2989ec4ec0762020-11-25T00:02:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6825510.1371/journal.pone.0068255The GTPase Rab37 Participates in the Control of Insulin Exocytosis.Sanda LjubicicPaola BezziSaska BrajkovicValeria NescaClaudiane GuayNorihiko OhbayashiMitsunori FukudaAmar AbderrhamaniRomano RegazziRab37 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.http://europepmc.org/articles/PMC3694898?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sanda Ljubicic Paola Bezzi Saska Brajkovic Valeria Nesca Claudiane Guay Norihiko Ohbayashi Mitsunori Fukuda Amar Abderrhamani Romano Regazzi |
spellingShingle |
Sanda Ljubicic Paola Bezzi Saska Brajkovic Valeria Nesca Claudiane Guay Norihiko Ohbayashi Mitsunori Fukuda Amar Abderrhamani Romano Regazzi The GTPase Rab37 Participates in the Control of Insulin Exocytosis. PLoS ONE |
author_facet |
Sanda Ljubicic Paola Bezzi Saska Brajkovic Valeria Nesca Claudiane Guay Norihiko Ohbayashi Mitsunori Fukuda Amar Abderrhamani Romano Regazzi |
author_sort |
Sanda Ljubicic |
title |
The GTPase Rab37 Participates in the Control of Insulin Exocytosis. |
title_short |
The GTPase Rab37 Participates in the Control of Insulin Exocytosis. |
title_full |
The GTPase Rab37 Participates in the Control of Insulin Exocytosis. |
title_fullStr |
The GTPase Rab37 Participates in the Control of Insulin Exocytosis. |
title_full_unstemmed |
The GTPase Rab37 Participates in the Control of Insulin Exocytosis. |
title_sort |
gtpase rab37 participates in the control of insulin exocytosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3694898?pdf=render |
work_keys_str_mv |
AT sandaljubicic thegtpaserab37participatesinthecontrolofinsulinexocytosis AT paolabezzi thegtpaserab37participatesinthecontrolofinsulinexocytosis AT saskabrajkovic thegtpaserab37participatesinthecontrolofinsulinexocytosis AT valerianesca thegtpaserab37participatesinthecontrolofinsulinexocytosis AT claudianeguay thegtpaserab37participatesinthecontrolofinsulinexocytosis AT norihikoohbayashi thegtpaserab37participatesinthecontrolofinsulinexocytosis AT mitsunorifukuda thegtpaserab37participatesinthecontrolofinsulinexocytosis AT amarabderrhamani thegtpaserab37participatesinthecontrolofinsulinexocytosis AT romanoregazzi thegtpaserab37participatesinthecontrolofinsulinexocytosis AT sandaljubicic gtpaserab37participatesinthecontrolofinsulinexocytosis AT paolabezzi gtpaserab37participatesinthecontrolofinsulinexocytosis AT saskabrajkovic gtpaserab37participatesinthecontrolofinsulinexocytosis AT valerianesca gtpaserab37participatesinthecontrolofinsulinexocytosis AT claudianeguay gtpaserab37participatesinthecontrolofinsulinexocytosis AT norihikoohbayashi gtpaserab37participatesinthecontrolofinsulinexocytosis AT mitsunorifukuda gtpaserab37participatesinthecontrolofinsulinexocytosis AT amarabderrhamani gtpaserab37participatesinthecontrolofinsulinexocytosis AT romanoregazzi gtpaserab37participatesinthecontrolofinsulinexocytosis |
_version_ |
1725439170911928320 |