IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation.
Fiche publication
Date publication
mai 2007
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHELLY Jamel, Dr VITALE Nicolas
Tous les auteurs :
Gambino F, Pavlowsky A, Béglé A, Dupont JL, Bahi N, Courjaret R, Gardette R, Hadjkacem H, Skala H, Poulain B, Chelly J, Vitale N, Humeau Y
Lien Pubmed
Résumé
Null mutations in the IL1-receptor accessory protein-like 1 gene (IL1RAPL1) are responsible for an inherited X-linked form of cognitive impairment. IL1RAPL1 protein physically interacts with neuronal calcium sensor-1 (NCS-1), but the functional impact of the IL1RAPL1/NCS-1 interaction remains unknown. Here, we demonstrate that stable expression of IL1RAPL1 in PC12 cells induces a specific silencing of N-type voltage-gated calcium channels (N-VGCC) activity that explains a secretion deficit observed in these IL1RAPL1 cells. Importantly, this modulation of VGCC activity is mediated by NCS-1. Indeed, a specific loss-of-function of N-VGCC was observed in PC12 cells overexpressing NCS-1, and a total recovery of N-VGCC activity was obtained by a down-regulation of NCS-1 in IL1RAPL1 cells. The functional relevance of the interaction between IL1RAPL1 and NCS-1 was also suggested by the reduction of neurite elongation observed in nerve growth factor (NGF)-treated IL1RAPL1 cells, a phenotype rescued by NCS-1 inactivation. Because both proteins are highly expressed in neurons, these results suggest that IL1RAPL1-related mental retardation could result from a disruption of N-VGCC and/or NCS-1-dependent synaptic and neuronal activities.
Mots clés
Animals, Calcium Channels, L-Type, metabolism, Cell Differentiation, drug effects, Electrophysiology, Gene Expression Regulation, Interleukin-1 Receptor Accessory Protein, genetics, Nerve Growth Factor, pharmacology, Neurites, drug effects, Neuronal Calcium-Sensor Proteins, genetics, Neuropeptides, genetics, PC12 Cells, Patch-Clamp Techniques, Rats
Référence
Proc. Natl. Acad. Sci. U.S.A.. 2007 May 22;104(21):9063-8