RT Journal Article SR Electronic T1 Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0092-16.2016 DO 10.1523/ENEURO.0092-16.2016 VO 3 IS 6 A1 Christopher M. Bartley A1 Rachel A. O’Keefe A1 Anna Blice-Baum A1 Mihaela-Rita Mihailescu A1 Xuan Gong A1 Laura Miyares A1 Esra Karaca A1 Angélique Bordey YR 2016 UL http://www.eneuro.org/content/3/6/ENEURO.0092-16.2016.abstract AB The fragile X mental retardation protein (FMRP) is an mRNA-binding regulator of protein translation that associates with 4-6% of brain transcripts and is central to neurodevelopment. Autism risk genes’ transcripts are overrepresented among FMRP-binding mRNAs, and FMRP loss-of-function mutations are responsible for fragile X syndrome, the most common cause of monogenetic autism. It is thought that FMRP-dependent translational repression is governed by the phosphorylation of serine residue 499 (S499). However, recent evidence suggests that S499 phosphorylation is not modulated by metabotropic glutamate receptor class I (mGluR-I) or protein phosphatase 2A (PP2A), two molecules shown to regulate FMRP translational repression. Moreover, the mammalian FMRP S499 kinase remains unknown. We found that casein kinase II (CK2) phosphorylates murine FMRP S499. Further, we show that phosphorylation of FMRP S499 permits phosphorylation of additional, nearby residues. Evidence suggests that these nearby residues are modulated by mGluR-I and PP2A pathways. These data support an alternative phosphodynamic model of FMRP that is harmonious with prior studies and serves as a framework for further investigation.