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Aβ 1–42 triggers the generation of a retrograde signaling complex from sentinel mRNA s in axons
Author(s) -
Walker Chandler A,
Randolph Lisa K,
Matute Carlos,
Alberdi Elena,
Baleriola Jimena,
Hengst Ulrich
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745435
Subject(s) - soma , axoplasmic transport , microbiology and biotechnology , translation (biology) , biology , neuroscience , retrograde signaling , axon , messenger rna , signal transduction , gene , genetics
Neurons frequently encounter neurodegenerative signals first in their periphery. For example, exposure of axons to oligomeric Aβ 1‐42 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 mRNA s in axons is induced within minutes of Aβ 1–42 addition in a Ca 2+ ‐dependent manner. This immediate protein synthesis following Aβ 1–42 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 Aβ 1–42 . These results establish that CNS axons react to neurodegenerative insults via the local translation of sentinel mRNA s encoding components of a retrograde signaling complex that transmit the information about the event to the neuronal soma.