Crucial role of neuron-enriched endosomal protein of 21 kDa in sorting between degradation and recycling of internalized G-protein-coupled receptors.
Recycling of endocytosed G-protein-coupled receptors involves a series of molecular events through early and recycling endosomes. The purpose of this work was to study the role of neuron-enriched endosomal protein of 21 kDa (NEEP21) in the recycling process of neurotensin receptors-1 and -2. Here we showed that suppression of NEEP21 expression does not modify the internalization rate of both receptors but strongly inhibited the recycling of the neurotensin receptor-2. In contrast, overexpression of NEEP21 changes the behavior of the neurotensin receptor-1 from a non-recycling to a recycling state. Recycling of the neurotensin receptor-2 involves both the phosphatidylinositol 3-kinase and the recycling endosome pathways, whereas recycling of the neurotensin receptor-1 induced by overexpression of NEEP21 only occurs by the phosphatidylinositol 3-kinase-dependent pathway. Taken together, these results confirm the essential role of NEEP21 in the recycling mechanism and show that this protein acts at the level of early endosomes to promote sorting of receptors toward a recycling pathway.
Debaigt
Colin
C
Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097 du Centre National de la Recherche Scientifique, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Hirling
Harald
H
Steiner
Pascal
P
Vincent
Jean-Pierre
JP
Mazella
Jean
J
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002465:Cell Movement; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism*; D014162:Transfection
D009419:Nerve Tissue Proteins; C461339:Nsg1 protein, rat; C099727:Ntsr2 protein, rat; D043562:Receptors, G-Protein-Coupled; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor