Conflict of interests: Multiple signal peptides with diverging goals

Venuto, Annunziata; Marco, Ario de

doi:10.1002/jcb.24393

Cited by 2 publications

(3 citation statements)

References 44 publications

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“…Since expression of either mCD8-GFP or nGFP alone does not display aggregated patterns, we speculate that the presence of two conflicting trafficking signals, signal peptide (SP) and NLS, present in the Casor might be a culprit for aggregate formation. In line with this, it is notable that normally a nuclear protein Myc accumulates in the cytoplasm if it is fused in frame with SP [38]. Expression of a fusion protein consisting of membrane-targeted myrGFP and RFP-NLS also produced aggregates in perinuclear region [39].…”

Section: Resultsmentioning

confidence: 99%

Identifying and monitoring neurons that undergo metamorphosis-regulated cell death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in Drosophila melanogaster

Lee

Kim

et al. 2017

Apoptosis

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Activation of caspases is an essential step toward initiating apoptotic cell death. During metamorphosis of Drosophila melanogaster, many larval neurons are programmed for elimination to establish an adult central nervous system (CNS) as well as peripheral nervous system (PNS). However, their neuronal functions have remained mostly unknown due to the lack of proper tools to identify them. To obtain detailed information about the neurochemical phenotypes of the doomed larval neurons and their timing of death, we generated a new GFP-based caspase sensor (Casor) that is designed to change its subcellular position from the cell membrane to the nucleus following proteolytic cleavage by active caspases. Ectopic expression of Casor in vCrz and bursicon, two different peptidergic neuronal groups that had been well-characterized for their metamorphic programmed cell death, showed clear nuclear translocation of Casor in a caspase-dependent manner before their death. We found similar events in some cholinergic neurons from both CNS and PNS. Moreover, Casor also reported significant caspase activities in the ventral and dorsal common excitatory larval motoneurons shortly after puparium formation. These motoneurons were previously unknown for their apoptotic fate. Unlike the events seen in the neurons, expression of Casor in non-neuronal cell types, such as glial cells and S2 cells, resulted in the formation of cytoplasmic aggregates, preventing its use as a caspase sensor in these cell types. Nonetheless, our results support Casor as a valuable molecular tool not only for identifying novel groups of neurons that become caspase-active during metamorphosis but also for monitoring developmental timing and cytological changes within the dying neurons.

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Section: Resultsmentioning

confidence: 99%

Identifying and monitoring neurons that undergo metamorphosis-regulated cell death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in Drosophila melanogaster

Lee

Kim

et al. 2017

Apoptosis

View full text Add to dashboard Cite

show abstract

“…However, despite some positive pre-clinical indications [35], [36], this transporter controls the shuttling of too many essential proteins to be considered an ideal therapeutic target. As an alternative possibility, the equilibrium between the two opposite fluxes could be modified by acting on the strength of the import/export motifs, as it happens in some pathological conditions [37].…”

Section: Discussionmentioning

confidence: 99%

“…In basic research, the effect of the rapid removal of cytoplasmic proteins has been evaluated by using single-domain antibodies that can trap GFP-tagged proteins and deliver them to ubiquitin-dependent degradation [39]. However, protein sub-cellular re-localization is not a straightforward application since artificially introduced sub-cellular localization sequences clash with native and discording signal sequences [40], a condition that can result in unpredictable protein distribution inside the cell [37]. Furthermore, physiological NES and NLS have apparently evolved as “weak” signals, whereas pathological motifs can be extremely more effective.…”

Section: Discussionmentioning

confidence: 99%