Differential Regulation of Syngap1 Translation by FMRP Modulates eEF2 Mediated Response on NMDAR Activity

Frontiers in Molecular Neuroscience
Abhik PaulJames P Clement

Abstract

SYNGAP1, a Synaptic Ras-GTPase activating protein, regulates synapse maturation during a critical developmental window. Heterozygous mutation in SYNGAP1 (SYNGAP1-/+) has been shown to cause Intellectual Disability (ID) in children. Recent studies have provided evidence for altered neuronal protein synthesis in a mouse model of Syngap1-/+. However, the molecular mechanism behind the same is unclear. Here, we report the reduced expression of a known translation regulator, FMRP, during a specific developmental period in Syngap1-/+ mice. Our results demonstrate that FMRP interacts with and regulates the translation of Syngap1 mRNA. We further show reduced Fmr1 translation leads to decreased FMRP level during development in Syngap1-/+ which results in an increase in Syngap1 translation. These developmental changes are reflected in the altered response of eEF2 phosphorylation downstream of NMDA Receptor (NMDAR)-mediated signaling. In this study, we propose a cross-talk between FMRP and SYNGAP1 mediated signaling which can also explain the compensatory effect of impaired signaling observed in Syngap1-/+ mice.

References

Aug 28, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mudit AgarwalCarl E Stafstrom
Oct 23, 2020·Molecular Biology Reports·Vijaya VermaJames P Clement

Citations

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Related Concepts

Study
GRIN1
Regulation of Synapse Maturation
SYNGAP1
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Regulation of Biological Process
FMR1
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