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Aβ1-42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons.
Walker CA
,
Randolph LK
,
Matute C
,
Alberdi E
,
Baleriola J
,
Hengst U
.
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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.
Baleriola,
Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions.
2014, Pubmed
Baleriola,
Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions.
2014,
Pubmed
Ben-Yaakov,
Axonal transcription factors signal retrogradely in lesioned peripheral nerve.
2012,
Pubmed
Demuro,
Calcium signaling and amyloid toxicity in Alzheimer disease.
2010,
Pubmed
Demuro,
Single-channel Ca(2+) imaging implicates Aβ1-42 amyloid pores in Alzheimer's disease pathology.
2011,
Pubmed
,
Xenbase
Gracias,
Local translation of TC10 is required for membrane expansion during axon outgrowth.
2014,
Pubmed
Gumy,
Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization.
2011,
Pubmed
Hanz,
Axoplasmic importins enable retrograde injury signaling in lesioned nerve.
2003,
Pubmed
Hengst,
Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein.
2009,
Pubmed
Hengst,
Functional and selective RNA interference in developing axons and growth cones.
2006,
Pubmed
Holt,
The central dogma decentralized: new perspectives on RNA function and local translation in neurons.
2013,
Pubmed
Jung,
Remote control of gene function by local translation.
2014,
Pubmed
Khan,
Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease.
2014,
Pubmed
Krstic,
Deciphering the mechanism underlying late-onset Alzheimer disease.
2013,
Pubmed
Kuchibhotla,
Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks.
2008,
Pubmed
Lacor,
Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease.
2007,
Pubmed
Levin,
Neuronal expression of vimentin in the Alzheimer's disease brain may be part of a generalized dendritic damage-response mechanism.
2009,
Pubmed
Liu,
Amyloid pathology is associated with progressive monoaminergic neurodegeneration in a transgenic mouse model of Alzheimer's disease.
2008,
Pubmed
Luo,
Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System.
2016,
Pubmed
Marcyniuk,
The topography of cell loss from locus caeruleus in Alzheimer's disease.
1986,
Pubmed
Pearson,
Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease.
1985,
Pubmed
Perlson,
Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve.
2005,
Pubmed
Perry,
Local translation in neuronal processes--in vivo tests of a "heretical hypothesis".
2014,
Pubmed
Resende,
Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death.
2008,
Pubmed
Saal,
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
2014,
Pubmed
Schmidt,
SUnSET, a nonradioactive method to monitor protein synthesis.
2009,
Pubmed
Selvaraj,
Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease.
2012,
Pubmed
Shigeoka,
Dynamic Axonal Translation in Developing and Mature Visual Circuits.
2016,
Pubmed
Taylor,
A microfluidic culture platform for CNS axonal injury, regeneration and transport.
2005,
Pubmed
Taylor,
Axonal translation of β-catenin regulates synaptic vesicle dynamics.
2013,
Pubmed
Taylor,
Axonal mRNA in uninjured and regenerating cortical mammalian axons.
2009,
Pubmed
Terenzio,
Locally translated mTOR controls axonal local translation in nerve injury.
2018,
Pubmed
Toepke,
PDMS absorption of small molecules and consequences in microfluidic applications.
2006,
Pubmed
Villarin,
Local synthesis of dynein cofactors matches retrograde transport to acutely changing demands.
2016,
Pubmed
Xu,
STAT3 Undergoes Acetylation-dependent Mitochondrial Translocation to Regulate Pyruvate Metabolism.
2016,
Pubmed
Yarmolinsky,
INHIBITION BY PUROMYCIN OF AMINO ACID INCORPORATION INTO PROTEIN.
1959,
Pubmed
Yoon,
Local translation of extranuclear lamin B promotes axon maintenance.
2012,
Pubmed
,
Xenbase
Yudin,
Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve.
2008,
Pubmed
Zhong,
Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6.
1994,
Pubmed
Zivraj,
Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.
2010,
Pubmed
,
Xenbase
