详细记录  
题名:The GTPase Rab37 Participates in the Control of Insulin Exocytosis.
作者:LJUBICIC S; BEZZI P; BRAJKOVIC S; NESCA V; GUAY C; OHBAYASHI N; FUKUDA M; ABDERRHAMANI A; REGAZZI R;
来源:PLoS One. 2013 Jun 27;8(6):e68255. Print 2013. [ IF= 4.09 ] ]
URL :10.1371/journal.pone.0068255
日期:20130131
摘要: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 beta-cells. In
agreement with these observations, we detected Rab37 in extracts of beta-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 beta-cells and
suggest that impaired expression of this GTPase may contribute to defective
insulin release in pre-diabetic and diabetic conditions.

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