axonal translation local protein synthesis RNA binding proteins RRID: AB_10805421 RRID: AB_2313703 RRID: AB_2661850 RRID: AB_476964 RRID: AB_528262
Local axonal protein synthesis plays a crucial role in the formation and function of neuronal circuits. Understanding the role of this mechanism in specific circuits requires identifying the protein composition and mRNA cargos of the ribonucleoprotein particles (RNPs) that form the substrate for axonal translation. FXGs (Fragile X granules) are axonal RNPs present in a stereotyped subset of mature axons in the intact brain that contain one or more of the Fragile X related (FXR) proteins (FMRP, FXR2P, and FXR1P) along with mRNA and ribosomes. Here we performed a systematic survey of the FXR protein composition and mRNA association of FXGs in the brain. We have identified four FXG types that can be categorized based on their FXR protein complement. All FXGs contain FXR2P, with FMRP and/or FXR1P present in circuit‐selective subsets. Individual neuronal cell types predominantly express a single FXG type, with FMRP‐containing FXGs the most prevalent in forebrain neurons. All FXG types associate with ribosomes and mRNA, but the specific mRNA cargos are a function of FXG type, brain region and neuron class. Transcripts for β‐catenin and its regulator APC associate with a subset of forebrain FXGs. Moreover, both these transcripts can colocalize within individual FXGs, suggesting that the axonal translation of functionally related proteins may be coordinately regulated with high spatiotemporal resolution. Cell type‐dependent expression of specific RNP types with distinct mRNA cargos, such as FXGs, presents a potential mechanism for regulating local translation and its output in a circuit‐dependent manner.
Fragile X granules (FXGs) are axonal mRNA granules that contain one or more of the Fragile X related (FXR) family of translational regulator proteins. Combined immunofluorescence and in situ hybridization revealed that FXGs exhibit circuit dependence in both the FXR proteins they contain and the mRNAs with which they associate.