Complexin I regulates glucose-induced secretion in pancreatic beta-cells.
The neuronal-specific protein complexin I (CPX I) plays an important role in controlling the Ca(2+)-dependent neurotransmitter release. Since insulin exocytosis and neurotransmitter release rely on similar molecular mechanisms and that pancreatic beta-cells and neuronal cells share the expression of many restricted genes, we investigated the potential role of CPX I in insulin-secreting cells. We found that pancreatic islets and several insulin-secreting cell lines express high levels of CPX I. The beta-cell expression of CPX I is mediated by the presence of a neuron restrictive silencer element located within the regulatory region of the gene. This element bound the transcriptional repressor REST, which is found in most cell types with the exception of mature neuronal cells and beta-cells. Overexpression of CPX I or silencing of the CPX I gene (Cplx1) by RNA interference led to strong impairment in beta-cell secretion in response to nutrients such as glucose, leucine and KCl. This effect was detected both in the early and the sustained secretory phases but was much more pronounced in the early phase. We conclude that CPX I plays a critical role in beta-cells in the control of the stimulated-exocytosis of insulin.
Abderrahmani
Amar
A
Department of Internal Medicine, University of Lausanne, Lausanne, Switzerland.
Niederhauser
Guy
G
Plaisance
Valérie
V
Roehrich
Marc-Estienne
ME
Lenain
Vincent
V
Coppola
Thierry
T
Regazzi
Romano
R
Waeber
Gérard
G
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D020868:Gene Silencing; D005947:Glucose / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
D033942:Adaptor Proteins, Vesicular Transport; D005947:Glucose; D019382:Human Growth Hormone; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C095992:complexin I