Aβ1-42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons

EMBO Reports
Chandler A WalkerUlrich Hengst

Abstract

Neurons frequently encounter neurodegenerative signals first in their periphery. For example, exposure of axons to oligomeric Aβ1-42 is sufficient to induce changes in the neuronal cell body that ultimately lead to degeneration. Currently, it is unclear how the information about the neurodegenerative insult is transmitted to the soma. Here, we find that the translation of pre-localized but normally silenced sentinel mRNAs in axons is induced within minutes of Aβ1-42 addition in a Ca2+-dependent manner. This immediate protein synthesis following Aβ1-42 exposure generates a retrograde signaling complex including vimentin. Inhibition of the immediate protein synthesis, knock-down of axonal vimentin synthesis, or inhibition of dynein-dependent transport to the soma prevented the normal cell body response to Aβ1-42 These results establish that CNS axons react to neurodegenerative insults via the local translation of sentinel mRNAs encoding components of a retrograde signaling complex that transmit the information about the event to the neuronal soma.

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Citations

Nov 22, 2020·International Journal of Molecular Sciences·Eloina Corradi, Marie-Laure Baudet
Dec 5, 2020·Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation·Pınar BormanMerve Denizli
Nov 17, 2020·Frontiers in Aging Neuroscience·Natalia SalvadoresFelipe A Court
Feb 3, 2021·Trends in Cell Biology·Loïc BroixLaurent Nguyen
May 4, 2020·Brain Research·Terika P SmithJeffery L Twiss
Apr 13, 2021·Progress in Neurobiology·Carla Perrone-CapanoMarianna Crispino
Jul 13, 2021·Frontiers in Cellular Neuroscience·Andres Di PaoloJosé Roberto Sotelo-Silveira
Jul 20, 2021·Frontiers in Integrative Neuroscience·María GamarraJimena Baleriola
Oct 27, 2021·Cellular and Molecular Life Sciences : CMLS·Lichao LiSheng-Jian Ji

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