A nuclear localization signal targets proteins to the retrograde transport system, thereby evading uptake into organelles in aplysia axons

Schmied, Robert; Ambron, Richard T.

doi:10.1002/(sici)1097-4695(199708)33:2<151::aid-neu4>3.0.co;2-1

Cited by 29 publications

(7 citation statements)

References 56 publications

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“…In contrast, nocodazole treatment reduced the number of incoming capsids reaching the neuronal nuclei ( Fig 7Bii ). Since importin α can contribute to retrograde axonal transport of some cargos [ 84 – 87 ], we also cultured DRG neurons in microfluidic chambers to selectively inoculate the neurons via the axons and not via the plasma membrane of the cell bodies for 4 h. However, nuclear targeting of HSV-1 capsids that in this experimental set-up was strictly dependent on axonal transport was as efficient in neurons expressing a scrambled shRNA ( Fig 7Dii ) as in neurons silenced for importin α1 expression ( Fig 7Eii ).…”

Section: Resultsmentioning

confidence: 99%

Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

et al. 2018

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Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4. While nuclear targeting of the incoming capsids, of the HSV-1 transcription activator VP16, and of the viral genomes were not affected, the nuclear import of the HSV-1 proteins ICP4 and ICP0, required for efficient viral transcription, and of ICP8 and pUL42, necessary for DNA replication, were reduced. Furthermore, quantitative electron microscopy showed that fibroblasts lacking importin α1 contained overall fewer nuclear capsids, but an increased proportion of mature nuclear capsids indicating that capsid formation and capsid egress into the cytoplasm were impaired. In neurons, importin α1 was also not required for nuclear targeting of incoming capsids, but for nuclear import of ICP4 and for the formation of nuclear capsid assembly compartments. Our data suggest that importin α1 is specifically required for the nuclear localization of several important HSV1 proteins, capsid assembly, and capsid egress into the cytoplasm, and may become rate limiting in situ upon infection at low multiplicity or in terminally differentiated cells such as neurons.

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Section: Resultsmentioning

confidence: 99%

Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

et al. 2018

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“…There is now accumulating evidence indicating that the transcription factors themselves can act as positive injury signals. Studies in the Aplysia mollusc have shown that NLS can target retrograde transport and nuclear uptake of heterologous proteins ( Schmied and Ambron, 1997 ). Although it was recently shown that protein kinase G (ApPKG) is activated at injury sites and retrogradely transported ( Sung et al, 2004 ), the mechanism responsible for injury-induced transport is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Sunday Driver links axonal transport to damage signaling

Cavalli

Kujala

Klumperman

et al. 2005

The Journal of Cell Biology

282

278

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Neurons transmit long-range biochemical signals between cell bodies and distant axonal sites or termini. To test the hypothesis that signaling molecules are hitchhikers on axonal vesicles, we focused on the c-Jun NH2-terminal kinase (JNK) scaffolding protein Sunday Driver (syd), which has been proposed to link the molecular motor protein kinesin-1 to axonal vesicles. We found that syd and JNK3 are present on vesicular structures in axons, are transported in both the anterograde and retrograde axonal transport pathways, and interact with kinesin-I and the dynactin complex. Nerve injury induces local activation of JNK, primarily within axons, and activated JNK and syd are then transported primarily retrogradely. In axons, syd and activated JNK colocalize with p150Glued, a subunit of the dynactin complex, and with dynein. Finally, we found that injury induces an enhanced interaction between syd and dynactin. Thus, a mobile axonal JNK–syd complex may generate a transport-dependent axonal damage surveillance system.

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“…In Aplysia, injection of axoplasm from injured nerves into naïve neurons triggers an injury‐like behavior accompanied by increased growth. The model proposed to explain this behavior has been that phosphorylation of injury signals exposes hidden nuclear localization signals (NLS), targeting them to the nucleus . The importance of retrograde transport of NLS‐containing proteins has been demonstrated later in rats, as injection of an NLS synthetic peptide into the injured nerve competes with the activation of intrinsic growth programs by preventing the retrograde transport of injury signals .…”

Section: Retrograde Transport Of Locally Activated Injury Signalsmentioning

confidence: 99%

Cell intrinsic control of axon regeneration

2014

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Although neurons execute a cell intrinsic program of axonal growth during development, following the establishment of connections, the developmental growth capacity declines. Besides environmental challenges, this switch largely accounts for the failure of adult central nervous system (CNS) axons to regenerate. Here, we discuss the cell intrinsic control of axon regeneration, including not only the regulation of transcriptional and epigenetic mechanisms, but also the modulation of local protein translation, retrograde and anterograde axonal transport, and microtubule dynamics. We further explore the causes underlying the failure of CNS neurons to mount a vigorous regenerative response, and the paradigms demonstrating the activation of cell intrinsic axon growth programs. Finally, we present potential mechanisms to support axon regeneration, as these may represent future therapeutic approaches to promote recovery following CNS injury and disease.

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A nuclear localization signal targets proteins to the retrograde transport system, thereby evading uptake into organelles in aplysia axons

Cited by 29 publications

References 56 publications

Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

Sunday Driver links axonal transport to damage signaling

Cell intrinsic control of axon regeneration

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