Publication

Distinguishing aggregate formation and aggregate clearance using cell-based assays

Eenjes, E., Dragich, J. M., Kampinga, H. H. & Yamamoto, A., 15-Mar-2016, In : Journal of Cell Science. 129, 6, p. 1260-1270 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

The accumulation of ubiquitylated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to a diminished aggregate burden, in terms of disease pathogenesis, the different approaches can have distinct outcomes. Using a novel cell-based assay that can distinguish newly formed versus preformed inclusions, we demonstrate that two proteins previously implicated in the autophagic clearance of expanded polyglutamine inclusions, HspB7 and Alfy (also known as WDFY3), actually affect very distinct cellular processes to affect aggregate burden. Using this cell-based assay, we also establish that constitutive expression of the aggregation-prone protein can measurably slow the elimination of protein aggregates, given that not all aggregates appear to be available for degradation. This new assay can therefore not only determine at what step amodifiermight influence aggregate burden, but also can be used to provide new insights into how protein aggregates are targeted for degradation.
Original languageEnglish
Pages (from-to)1260-1270
Number of pages11
JournalJournal of Cell Science
Volume129
Issue number6
Publication statusPublished - 15-Mar-2016

    Keywords

  • Protein aggregation, Polyglutamine protein, Chaperone, Autophagy, UBIQUITIN-PROTEASOME SYSTEM, AUTOPHAGIC DEGRADATION, HUNTINGTONS-DISEASE, SELECTIVE AUTOPHAGY, PROTEIN AGGREGATION, INCLUSION-BODIES, PRONE PROTEINS, IN-VIVO, POLYGLUTAMINE, ALFY

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