Neurotensin receptor-2 and -3 are crucial for the anti-apoptotic effect of neurotensin on pancreatic beta-TC3 cells.
The neuropeptide neurotensin (NT) has been recently shown to protect pancreatic beta cells from toxic agents-induced apoptosis through interaction with the NT receptor-2 (NTSR2) and activation of the phosphatidylinositol-3 kinase pathway. However, expression of the NT receptor-3/sortilin (NTSR3) in the mouse pancreatic beta cell line -TC3 led us to investigate its possible functional role in these cells. By using siRNA, immunoprecipitation, co-localization and caspase-3 assays,we provide evidence for a functional endogenous interaction between NTSR2 and NTSR3. Expression of both receptors is necessary for the protective action of NT on staurosporine-induced caspase-3 activity in -TC3 cells. Moreover, NTSR2 and NTSR3 co-immunoprecipitate and are co-localized at the plasma membrane. Thus, the NT response in beta cells is controlled by the formation of a functional complex between NTSR2 and NTSR3.
Béraud-Dufour
Sophie
S
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, UMR 6097, Université de Nice Sophia Antipolis, 660 route des Lucioles, 06560 Valbonne, France.
Coppola
Thierry
T
Massa
Fabienne
F
Mazella
Jean
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D019610:Cytoprotection; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009496:Neurotensin / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D018028:Receptors, Neurotensin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine / Q000378:metabolism
C490984:Ntsr2 protein, mouse; D034741:RNA, Small Interfering; D018028:Receptors, Neurotensin; C426065:neurotensin receptor NTR-3; D009496:Neurotensin; D019869:Phosphatidylinositol 3-Kinases; D053148:Caspase 3; D019311:Staurosporine