Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line.
OBJECTIVE
The neuropeptide neurotensin (NT) exerts its intracellular effect by interacting with 3 different receptors. Two of these receptors (NTR1 and NTR2) belong to the G protein-coupled receptor family, whereas the third one (NTR3) is a type I receptor with a single transmembrane domain. We recently showed that the 2 structurally different receptors NTR1 and NTR3 were coexpressed in several human cancer cells on which NT exerts proliferative effects.


METHODS
Here, by an immunoprecipitation approach, we provide biochemical evidence for an endogenous heterodimerization of the G protein-coupled receptor NTR1 with the NTR3 in the human adenocarcinoma cell line HT29.


RESULTS
We show that both receptors are expressed and colocalized within the cell surface of HT29 cells where they already interact to form a heterodimer. The NTR1-NTR3 complex is then internalized on NT stimulation.


CONCLUSIONS
The complex formed between these 2 structurally unrelated NT receptors modulates both the NT-induced phosphorylation of mitogen-activated protein kinases and the phosphoinositide (PI) turnover mediated by the NTR1.
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019281:Dimerization; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D019073:HT29 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009496:Neurotensin / Q000378:metabolism*; D010766:Phosphorylation; D018028:Receptors, Neurotensin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009496:Neurotensin; D018028:Receptors, Neurotensin; D000099183:Sortilin