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Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain

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  • Additional Information
    • Publication Information:
      American Association for the Advancement of Science (AAAS), 2021.
    • Publication Date:
      2021
    • Abstract:
      Rhes ( RASD2 ) is a thyroid hormone–induced gene that regulates striatal motor activity and promotes neurodegeneration in Huntington disease (HD) and tauopathy. Rhes moves and transports the HD protein, polyglutamine-expanded huntingtin (mHTT), via tunneling nanotube (TNT)–like membranous protrusions between cultured neurons. However, similar intercellular Rhes transportation in the intact brain was unknown. Here, we report that Rhes induces TNT-like protrusions in the striatal medium spiny neurons (MSNs) and transported between dopamine-1 receptor (D1R)–MSNs and D2R-MSNs of intact striatum and organotypic brain slices. Notably, mHTT is robustly transported within the striatum and from the striatum to the cortical areas in the brain, and Rhes deletion diminishes such transport. Moreover, Rhes moves to the cortical regions following restricted expression in the MSNs of the striatum. Thus, Rhes is a first striatum-enriched protein demonstrated to move and transport mHTT between neurons and brain regions, providing new insights into interneuronal protein transport in the brain.
    • ISSN:
      2375-2548
    • Accession Number:
      10.1126/sciadv.abm3877
    • Accession Number:
      10.1101/2021.08.27.457956
    • Rights:
      URL: http://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
    • Accession Number:
      edsair.doi.dedup.....7bd4cd08f8727a3626e7f43a40ab39b7