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PLoS One. 2014 May 7;9(5):e96956. doi: 10.1371/journal.pone.0096956. eCollection 2014.

FMRP S499 is phosphorylated independent of mTORC1-S6K1 activity.

Author information

1
Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Medical Scientist Training Program, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
2
Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Abstract

Hyperactive mammalian target of rapamycin (mTOR) is associated with cognitive deficits in several neurological disorders including tuberous sclerosis complex (TSC). The phosphorylation of the mRNA-binding protein FMRP reportedly depends on mTOR complex 1 (mTORC1) activity via p70 S6 kinase 1 (S6K1). Because this phosphorylation is thought to regulate the translation of messages important for synaptic plasticity, we explored whether FMRP phosphorylation of the S6K1-dependent residue (S499) is altered in TSC and states of dysregulated TSC-mTORC1 signaling. Surprisingly, we found that FMRP S499 phosphorylation was unchanged in heterozygous and conditional Tsc1 knockout mice despite significantly elevated mTORC1-S6K1 activity. Neither up- nor down-regulation of the mTORC1-S6K1 axis in vivo or in vitro had any effect on phospho-FMRP S499 levels. In addition, FMRP S499 phosphorylation was unaltered in S6K1-knockout mice. Collectively, these data strongly suggest that FMRP S499 phosphorylation is independent of mTORC1-S6K1 activity and is not altered in TSC.

PMID:
24806451
PMCID:
PMC4013076
DOI:
10.1371/journal.pone.0096956
[Indexed for MEDLINE]
Free PMC Article

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