Fragile X granules are a family of axonal ribonucleoprotein particles with circuit-dependent protein composition and mRNA cargos

The Journal of Comparative Neurology
Eunice ChyungMichael R Akins

Abstract

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 c...Continue Reading

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Citations

Jun 12, 2020·The FEBS Journal·Mohamed S TahaMohammad R Ahmadian
Jan 19, 2019·Brain Sciences·Rachel Michelle SaréCarolyn Beebe Smith
May 23, 2019·Cell Death and Differentiation·Chuyu HuangZhenguo Chen
Aug 29, 2018·Brain Plasticity·Natalie E PatzlaffXinyu Zhao
Sep 11, 2019·The Journal of Comparative Neurology·Katherine A ShepardMichael R Akins
Mar 22, 2019·Neuron·Claudia Bagni, R Suzanne Zukin
Apr 13, 2021·Progress in Neurobiology·Carla Perrone-CapanoMarianna Crispino

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