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The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth.
Glia 2019GLIA

Abstract

During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with myelin. The highly polarized oligodendrocytes generate myelin sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote myelin sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for myelin sheath development, we examined fmr1-/- mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1-/- mutants developed myelin sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential myelin protein, was reduced in myelin tracts of fmr1-/- mutants, but loss of FMRP function did not impact the localization of mbpa transcript in myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1-/- mutant sheath growth and induced short myelin sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes sheath growth through local regulation of translation.

Authors+Show Affiliations

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31626382

Citation

Doll, Caleb A., et al. "The RNA Binding Protein Fragile X Mental Retardation Protein Promotes Myelin Sheath Growth." Glia, 2019.
Doll CA, Yergert KM, Appel BH. The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth. Glia. 2019.
Doll, C. A., Yergert, K. M., & Appel, B. H. (2019). The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth. Glia, doi:10.1002/glia.23731.
Doll CA, Yergert KM, Appel BH. The RNA Binding Protein Fragile X Mental Retardation Protein Promotes Myelin Sheath Growth. Glia. 2019 Oct 18; PubMed PMID: 31626382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth. AU - Doll,Caleb A, AU - Yergert,Katie M, AU - Appel,Bruce H, Y1 - 2019/10/18/ PY - 2019/06/18/received PY - 2019/09/20/revised PY - 2019/09/22/accepted PY - 2019/10/19/entrez PY - 2019/10/19/pubmed PY - 2019/10/19/medline KW - RNA binding protein KW - fragile X mental retardation protein KW - messenger RNA KW - myelin KW - oligodendrocyte KW - spinal cord KW - zebrafish JF - Glia JO - Glia N2 - During development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with myelin. The highly polarized oligodendrocytes generate myelin sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote myelin sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for myelin sheath development, we examined fmr1-/- mutant zebrafish and drove FMR1 expression specifically in oligodendrocytes. We found oligodendrocytes in fmr1-/- mutants developed myelin sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes with FMR1 expression. Myelin basic protein (Mbp), an essential myelin protein, was reduced in myelin tracts of fmr1-/- mutants, but loss of FMRP function did not impact the localization of mbpa transcript in myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescue fmr1-/- mutant sheath growth and induced short myelin sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes sheath growth through local regulation of translation. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/31626382/The_RNA_binding_protein_fragile_X_mental_retardation_protein_promotes_myelin_sheath_growth_ L2 - https://doi.org/10.1002/glia.23731 DB - PRIME DP - Unbound Medicine ER -