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USP19 increases the amount of TARDBP. 11 / 11
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"Interestingly, Xu et al., (2018) also observed that co-expression of USP19 with wild type TDP-43, barely increased the amount of TDP-43 in the extracellular medium [28]."
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"Conversely, when co-expressed with the pathological TDP-43-K263E (Fig. 1b), USP19-WT, but not the USP19-ΔTM, significantly increased the secretion of aggregated TDP-43 (Fig. 1d, e)."
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"Interestingly, when the same experiments were conducted with the C-terminus prion-like domain (GFP-TDP-43-CTF ) prone to high aggregation [35] (see Fig. S3a), neither USP19-WT nor its mutants stimulated TDP-43 secretion (Fig. S3d)."
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"The data presented above revealed that USP19-WT promotes the secretion of misfolded TDP-43 but the mechanisms by which USP19-WT induces this secretion are still unresolved."
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"The vesicular SNARE VAMP7 regulates the secretion of misfolded TDP-43 mediated by USP19."
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"The DNAJC5/CSPalpha chaperone protein modulates the release of TDP-43 aggregates mediated by USP19."
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"USP19 overexpression promotes the secretion of soluble and free TDP-43 aggregates."
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"This indicates that USP19 does not promote the release of misfolded TDP-43 through the exosomal pathway."
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"The fact that TDP-43 was found to be released in a VAMP7-dependent manner is certainly coherent with this notion.In our study, we observed that inhibiting DNAJC5/CSPα function using a dominant negative construct (S10A-CSPα), or through DNAJC5/CSPα siRNAs, significantly reduced the release of misfolded TDP-43 mediated by USP19."
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"Nevertheless, the implication of early autophagy processes was further supported by a significant decrease in USP19-mediated misfolded TDP-43 secretion upon inhibition of ATG7, RAB11A or VAMP7 components, all of which are involved in the early steps of phagophore/autophagosome biogenesis [47, 59, 70]."
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"Here we found that USP19 overexpression significantly promotes the secretion of soluble and aggregated misfolded TDP-43, requiring both ER anchoring and ubiquitin peptidase activity."
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