TitleDifferential Regulation of Translation by FMRP Modulates eEF2 Mediated Response on NMDAR Activity.
Publication TypeJournal Article
Year of Publication2019
AuthorsPaul A, Nawalpuri B, Shah D, Sateesh S, Muddashetty RS, Clement JP
JournalFront Mol Neurosci
Date Published2019

SYNGAP1, a Synaptic Ras-GTPase activating protein, regulates synapse maturation during a critical developmental window. Heterozygous mutation in () 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 . 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 mice. Our results demonstrate that FMRP interacts with and regulates the translation of mRNA. We further show reduced translation leads to decreased FMRP level during development in which results in an increase in 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 mice.

Alternate JournalFront Mol Neurosci
PubMed ID31143100
PubMed Central IDPMC6520660