PT - JOURNAL ARTICLE AU - Christopher M. Bartley AU - Rachel A. O’Keefe AU - Anna Blice-Baum AU - Mihaela-Rita Mihailescu AU - Xuan Gong AU - Laura Miyares AU - Esra Karaca AU - Angélique Bordey TI - Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP AID - 10.1523/ENEURO.0092-16.2016 DP - 2016 Nov 01 TA - eneuro PG - ENEURO.0092-16.2016 VI - 3 IP - 6 4099 - http://www.eneuro.org/content/3/6/ENEURO.0092-16.2016.short 4100 - http://www.eneuro.org/content/3/6/ENEURO.0092-16.2016.full SO - eNeuro2016 Nov 01; 3 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.