caa a22 4500 606174842 CHVBK 20210128100740.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00018-015-1943-x doi (NATIONALLICENCE)springer-10.1007/s00018-015-1943-x The function of RNA-binding proteins at the synapse: implications for neurodegeneration [Elektronische Daten] [Chantelle Sephton, Gang Yu] The loss of synapses is a central event in neurodegenerative diseases. Synaptic proteins are often associated with disease neuropathology, but their role in synaptic loss is not fully understood. Of the many processes involved in sustaining the integrity of synapses, local protein translation can directly impact synaptic formation, communication, and maintenance. RNA-binding proteins and their association with RNA granules serve to regulate mRNA transportation and translation at synapses and in turn regulate the synapse. Genetic mutations in RNA-binding proteins FUS and TDP-43 have been linked with causing neurodegenerative diseases: amyotrophic lateral sclerosis and frontotemporal dementia. The observation that mutations in FUS and TDP-43 coincide with changes in RNA granules provides evidence that dysfunction of RNA metabolism may underlie the mechanism of synaptic loss in these diseases. However, we do not know how mutations in RNA-binding proteins would affect RNA granule dynamics and local translation, or if these alterations would cause neurodegeneration. Further investigation into this area will lead to important insights into how disruption of RNA metabolism and local translation at synapses can cause neurodegenerative diseases. The Author(s), 2015 Amyotrophic lateral sclerosis nationallicence Frontotemporal dementia nationallicence Local translation nationallicence RNA granules nationallicence RNP granules nationallicence Stress granules nationallicence FUS nationallicence TDP-43 nationallicence ALS : Amyotrophic lateral sclerosis nationallicence AMPA : α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid nationallicence CPEB : Cytoplasmic polyadenylation element-binding protein nationallicence FTD : Frontotemporal dementia nationallicence FMRP : Fragile X mental retardation protein 1 nationallicence FUS : Fused in sarcoma nationallicence hnRNP : Heterogeneous nuclear ribonucleoprotein nationallicence mGluR : Metabotropic glutamate receptor nationallicence NES : Nuclear export signal nationallicence NLS : Nuclear localization signal nationallicence PSD-95 : Postsynaptic density protein 95 nationallicence PY-NLS : Proline-tyrosine nuclear localization signal nationallicence RISC : RNA-induced silencing complex nationallicence RGG : Arginine-glycine-glycine nationallicence RNP : Ribonucleoprotein particles nationallicence RRM : RNA recognition motif nationallicence TDP-43 : Transactive response DNA-binding protein 43 nationallicence tRNP : Transport ribonucleoprotein particles nationallicence UTR : Untranslated region nationallicence ZBP1 : Zipcode-binding protein 1 nationallicence Sephton Chantelle Department of Psychiatry and Neuroscience, Institut Universitaire En Santé Mentale de Québec, Université Laval, G1J 2G3, Quebec, QC, Canada aut Yu Gang Department of Neuroscience, University of Texas Southwestern Medical Center, 75390, Dallas, TX, USA aut Cellular and Molecular Life Sciences Springer Basel 72/19(2015-10-01), 3621-3635 1420-682X 72:19<3621 2015 72 18 https://doi.org/10.1007/s00018-015-1943-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1943-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sephton Chantelle Department of Psychiatry and Neuroscience, Institut Universitaire En Santé Mentale de Québec, Université Laval, G1J 2G3, Quebec, QC, Canada aut NATIONALLICENCE 700 1- Yu Gang Department of Neuroscience, University of Texas Southwestern Medical Center, 75390, Dallas, TX, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/19(2015-10-01), 3621-3635 1420-682X 72:19<3621 2015 72 18