IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation

F. Gambino, A. Pavlowsky, A. Begle, J.-L. Dupont, N. Bahi, R. Courjaret, R. Gardette, H. Hadjkacem, H. Skala, B. Poulain, J. Chelly, N. Vitale, Y. Humeau
Proceedings of the National Academy of Sciences. 2007-05-14; 104(21): 9063-9068
DOI: 10.1073/pnas.0701133104

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1. Proc Natl Acad Sci U S A. 2007 May 22;104(21):9063-8. Epub 2007 May 14.

IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive
functions, regulates N-type Ca2+-channel and neurite elongation.

Gambino F(1), Pavlowsky A, Béglé A, Dupont JL, Bahi N, Courjaret R, Gardette R,
Hadjkacem H, Skala H, Poulain B, Chelly J, Vitale N, Humeau Y.

Author information:
(1)Département Neurotransmission et Sécrétion Neuroendocrine, Institut des
Neurosciences Cellulaires et Intégratives, Université Louis Pasteur, 5 Rue Blaise
Pascal, 67084 Strasbourg, France.

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.

DOI: 10.1073/pnas.0701133104
PMCID: PMC1885628
PMID: 17502602 [Indexed for MEDLINE]


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