title: NTS2 modulates the intracellular distribution and trafficking of NTS1 via heterodimerization.
abstract: Neurotensin (NT) receptors NTS1 and NTS2 are known to display considerable distributional overlap in mammalian central nervous system (CNS). Using co-immunoprecipitation approaches, we demonstrated here that NTS1 forms constitutive heterodimers with NTS2 in transfected COS-7 cells. We also showed that co-expression of NTS2 with NTS1 markedly decreases the cell surface density of NTS1 without affecting ERK1/2 MAPK activity or NT-induced NTS1 internalization. However, radioligand-binding studies indicated that upon prolonged NT stimulation, cell surface NTS1 receptors are more resistant to down-regulation in cells co-expressing NTS1 and NTS2 than in cells expressing NTS1 alone. Taken together, these data suggest that NTS1/NTS2 heterodimerization affects the intracellular distribution and trafficking of NTS1 by making it more similar to that of NTS2 as witnessed in cells expressing NTS2 alone. NTS1/NTS2 heterodimerization might therefore represent an additional mechanism in the regulation of NT-triggered responses mediated by NTS1 and NTS2 receptors.
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada H3A 2B4.
authors.forename: Amélie
authors.initials: A
authors.lastname: Perron
authors.forename: Nadder
authors.initials: N
authors.lastname: Sharif
authors.forename: Philippe
authors.initials: P
authors.lastname: Sarret
authors.forename: Thomas
authors.initials: T
authors.lastname: Stroh
authors.forename: Alain
authors.initials: A
authors.lastname: Beaudet
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D015536:Down-Regulation; D020935:MAP Kinase Signaling System / Q000502:physiology; D018613:Microscopy, Confocal; D021381:Protein Transport; D051381:Rats; D018028:Receptors, Neurotensin / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection
chemical_list: C099727:Ntsr2 protein, rat; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor