The coffin-lowry syndrome-associated protein RSK2 and neurosecretion

M. Zeniou-Meyer, F. Gambino, Mohamed-Raafet Ammar, Y. Humeau, N. Vitale
Cell Mol Neurobiol. 2010-11-01; 30(8): 1401-1406
DOI: 10.1007/s10571-010-9578-9

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1. Cell Mol Neurobiol. 2010 Nov;30(8):1401-6. doi: 10.1007/s10571-010-9578-9.

The Coffin-Lowry syndrome-associated protein RSK2 and neurosecretion.

Zeniou-Meyer M(1), Gambino F, Ammar MR, Humeau Y, Vitale N.

Author information:
(1)Département Neurotransmission and Sécrétion Neuroendocrine, Institut des
Neurosciences Cellulaires et Intégratives (UPR-3212), Centre National de
Recherche Scientifique and Université de Strasbourg, 5 rue Blaise Pascal, 67084
Strasbourg, France.

Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation,
characterized in male patients by psychomotor and growth retardation and various
skeletal anomalies. CLS is caused by mutations in the RPS6KA3 gene, which encodes
RSK2, a growth factor-regulated protein kinase. Cognitive deficiencies in CLS
patients are prominent, but markedly variable in severity, even between siblings.
However, the vast majority of patients are severely affected, with mental
retardation ranging from moderate to profound. We used a RSK2-KO mouse model that
shows no obvious brain abnormalities at the anatomical and histological levels to
study the function of RSK2 in neurosecretion. Behavioral studies revealed normal
motor coordination, but a profound retardation in spatial learning and a deficit
in long-term spatial memory, providing evidence that RSK2 plays similar roles in
mental functioning both in mice and human. We found that associative LTP at
cortical inputs to the lateral amygdala was blocked in Rsk2 KO mice. Using an RNA
interference rescue strategy in PC12 cells, we were able to demonstrate that RSK2
regulates catecholamine release through the phosphorylation of PLD. These results
provide the first molecular evidence that RSK2 could regulate neurotransmitter
release by activating PLD production of lipids required for exocytosis.

DOI: 10.1007/s10571-010-9578-9
PMID: 21061166 [Indexed for MEDLINE]


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