Distinguishing aggregate formation and aggregate clearance using cell-based assays

Journal of Cell Science
Evelien EenjesAi Yamamoto

Abstract

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 a modifier might influence aggregate burden, but also can be used to provide new insights into how protein aggregates are targeted for degradation.

References

Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KazantsevD Housman
Dec 21, 2000·Trends in Cell Biology·R R Kopito
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Jun 28, 2005·Nature Genetics·Brinda RavikumarDavid C Rubinsztein
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Atsushi IwataRon R Kopito
Sep 30, 2005·The Journal of Biological Chemistry·Atsushi IwataRon R Kopito
Mar 1, 2006·The Journal of Cell Biology·Ai YamamotoJames E Rothman
Dec 7, 2006·PLoS Biology·María A RujanoHarm H Kampinga
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Sep 6, 2007·Autophagy·Akiko Kuma, Noboru Mizushima
Jun 7, 2008·ACS Chemical Biology·Georgyi V LosKeith V Wood
Feb 17, 2009·The Journal of Biological Chemistry·Atsushi IwataShoji Tsuji
Mar 3, 2009·Molecular Cell·Vladimir KirkinTerje Johansen
May 26, 2009·Biochimica Et Biophysica Acta·Michel J VosHarm H Kampinga
Oct 3, 2009·Journal of Neuroscience Research·Makoto UrushitaniIkuo Tooyama
Dec 23, 2009·The Journal of Cell Biology·Leslie Michels ThompsonJoan S Steffan
Mar 5, 2010·The Journal of Biological Chemistry·Sally K MakDonato A Di Monte
Sep 17, 2010·Human Molecular Genetics·Michel J VosHarm H Kampinga
Sep 25, 2010·Journal of Molecular and Cellular Cardiology·Huali ZhangIvor J Benjamin
Apr 21, 2012·International Journal of Cell Biology·Trond Lamark, Terje Johansen
Aug 10, 2012·Autophagy·Dalibor MijaljicaRodney J Devenish
Aug 29, 2012·Future Medicinal Chemistry·Christopher W JohnsonAi Yamamoto
Nov 28, 2012·Journal of Cell Science·Jelena KoracIvan Dikic
Aug 3, 2013·The Journal of Biological Chemistry·Katrin JuenemannEric A J Reits
Mar 19, 2014·Cell Death and Differentiation·E-J BaeS-J Lee
Oct 18, 2014·Frontiers in Molecular Neuroscience·Zaira Ortega, Jose J Lucas

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Citations

Feb 27, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guan-Ting LiuChung-Pei Lee
May 18, 2019·The Journal of Biological Chemistry·Di WuHarm H Kampinga
Sep 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zoe MputhiaPrashant Bharadwaj
Oct 28, 2018·Acta Neuropathologica Communications·Urmi SenguptaRakez Kayed
Apr 24, 2020·Cell Stress & Chaperones·Leen VendredyVincent Timmerman
Oct 14, 2018·Nature Communications·Anne F J JanssenLukas C Kapitein
Aug 28, 2018·Neurobiology of Disease·Katherine R Croce, Ai Yamamoto
Mar 24, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Katherine R Croce, Ai Yamamoto
Apr 9, 2021·Biochemistry. Biokhimii︠a︡·Lydia K MuranovaNikolai B Gusev
Nov 3, 2016·Journal of Cell Science·Stephanie Wales TobinJohn C McDermott
Jan 30, 2018·ACS Chemical Neuroscience·Filippa Lo Cascio, Rakez Kayed

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