FMRP S499 Is Phosphorylated Independent of mTORC1-S6K1 Activity |
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| Authors: | Christopher M Bartley Rachel A O’Keefe Angélique Bordey |
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| Institution: | 1. Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.; 2. Medical Scientist Training Program, Yale University School of Medicine, New Haven, Connecticut, United States of America.; 3. Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.; Université de Technologie de Compiègne, France, |
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| 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. |
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