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Cellular and Molecular Neurobiology

, Volume 30, Issue 8, pp 1401–1406 | Cite as

The Coffin-Lowry Syndrome-Associated Protein rsk2 and Neurosecretion

  • M. Zeniou-Meyer
  • F. Gambino
  • Mohamed-Raafet Ammar
  • Y. Humeau
  • N. Vitale
Report

Abstract

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.

Keywords

RSK2 Exocytosis PLD Mental retardation Coffin-Lowry syndrome 

Notes

Acknowledgments

We wish to thank Dr André Hanauer for providing us with the RSK2 KO mice and Drs Jens Rettig and Ute Becherer for the capacitance recording of bovine chromaffin cells. We wish to thank Dr Nancy Grant for critical reading of the manuscript. This work was supported by ANR grants (ANR-09-BLAN-0264-01) to NV and (ANR-06-003-Neuro-01) to YH.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • M. Zeniou-Meyer
    • 1
  • F. Gambino
    • 1
  • Mohamed-Raafet Ammar
    • 1
  • Y. Humeau
    • 1
  • N. Vitale
    • 1
  1. 1.Département Neurotransmission and Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives (UPR-3212)Centre National de la Recherche Scientifique and Université de StrasbourgStrasbourgFrance

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