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Mol Brain. 2019 Jul 10;12(1):65. doi: 10.1186/s13041-019-0473-0.

NMDAR mediated translation at the synapse is regulated by MOV10 and FMRP.

Author information

1
Centre for Brain Development and Repair (CBDR), Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India.
2
School of Chemical and Biotechnology, Shanmugha Arts, Science and Technology & Research Academy (SASTRA) University, Thanjavur, 613401, India.
3
The University of Trans-Disciplinary Health Sciences and Technology, Bangalore, 560064, India.
4
National Centre for Biological Sciences (NCBS), Bangalore, 560065, India.
5
Centre for Discovery Brain Sciences, Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, EH89XD, UK.
6
Centre for Brain Development and Repair (CBDR), Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, 560065, India. ravism@instem.res.in.

Abstract

Protein synthesis is crucial for maintaining synaptic plasticity and synaptic signalling. Here we have attempted to understand the role of RNA binding proteins, Fragile X Mental Retardation Protein (FMRP) and Moloney Leukemia Virus 10 (MOV10) protein in N-Methyl-D-Aspartate Receptor (NMDAR) mediated translation regulation. We show that FMRP is required for translation downstream of NMDAR stimulation and MOV10 is the key specificity factor in this process. In rat cortical synaptoneurosomes, MOV10 in association with FMRP and Argonaute 2 (AGO2) forms the inhibitory complex on a subset of NMDAR responsive mRNAs. On NMDAR stimulation, MOV10 dissociates from AGO2 and promotes the translation of its target mRNAs. FMRP is required to form MOV10-AGO2 inhibitory complex and to promote translation of MOV10 associated mRNAs. Phosphorylation of FMRP appears to be the potential switch for NMDAR mediated translation and in the absence of FMRP, the distinct translation response to NMDAR stimulation is lost. Thus, FMRP and MOV10 have an important regulatory role in NMDAR mediated translation at the synapse.

KEYWORDS:

FMRP/MOV10/NMDAR mediated translation

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