Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation

Acta Neuropathologica
Marcel KunadtAnja Schneider

Abstract

Extracellular α-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How α-Synuclein is released into the extracellular space is still unclear. Here, we show that α-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of α-Synuclein in extracellular vesicles is regulated by sumoylation and that sumoylation acts as a sorting factor for targeting of both, cytosolic and transmembrane proteins, to extracellular vesicles. We provide evidence that the SUMO-dependent sorting utilizes the endosomal sorting complex required for transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo proteins is so far the only known determinant for ESCRT-dependent sorting into the extracellular vesicle pathway. Our study reveals a function of SUMO protein modification as a Ubiquitin-independent ESCRT sorting signal, regulating the extracellular vesicle release of α-Synuclein. We deciphered in detail the molecular mechanism which directs α-Synuclein into extracellular vesicles which is of highest relevance for the understanding of Parkinson's disease pathogenesis and progression at the molecular level. We furthermore propose that sumo-...Continue Reading

References

May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G SpillantiniM Goedert
Oct 14, 2000·Annual Review of Cell and Developmental Biology·F Melchior
Jan 17, 2002·Cell·Andrea PichlerFrauke Melchior
Dec 25, 2002·Neurobiology of Aging·Heiko BraakEva Braak
Aug 2, 2003·Current Opinion in Cell Biology·Camilla RaiborgHarald Stenmark
Jul 13, 2004·Analytical Biochemistry·Yasuhiro UchimuraHisato Saitoh
Jun 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·He-Jin LeeSeung-Jae Lee
Jun 28, 2005·Biochemical and Biophysical Research Communications·Armin GieseHans Kretzschmar
Mar 10, 2006·The Journal of Biological Chemistry·Christina-Maria HeckerIvan Dikic
Jul 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lawrence RajendranKai Simons
Nov 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eva-Maria Krämer-AlbersKlaus-Armin Nave
May 1, 2007·Journal of Molecular Biology·Allan D Capili, Christopher D Lima
May 12, 2007·The EMBO Journal·Puck KnipscheerTitia K Sixma
Nov 15, 2007·Nature Reviews. Molecular Cell Biology·Ruth Geiss-Friedlander, Frauke Melchior
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Gerrit van MeerGerald W Feigenson
Mar 1, 2008·Science·Katarina TrajkovicMikael Simons
Apr 3, 2008·PloS One·Tiago Fleming OuteiroPamela J McLean
Aug 22, 2008·Neurobiology of Aging·Evangelia EmmanouilidouKostas Vekrellis
Feb 17, 2009·Molecular Cell·Per Stehmeier, Stefan Muller
May 16, 2009·Current Opinion in Cell Biology·Mikael Simons, Graça Raposo
Aug 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Paula DesplatsSeung-Jae Lee
Sep 30, 2009·Experimental Neurology·Jeffrey H Kordower, Patrik Brundin
Jan 13, 2010·Neuron·Adriano Aguzzi, Lawrence Rajendran
May 21, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Evangelia EmmanouilidouKostas Vekrellis
Jun 18, 2010·The Journal of Biological Chemistry·Katrin StraussAnja Schneider
Sep 2, 2010·The Journal of Biological Chemistry·Takashi NonakaMasato Hasegawa
Sep 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Karin M DanzerPamela J McLean
Jan 20, 2011·The Journal of Clinical Investigation·Christian HansenPatrik Brundin
Feb 9, 2011·The Journal of Biological Chemistry·Beiyi ShenStephen J Gould
Feb 10, 2011·Neurobiology of Disease·Lydia Alvarez-ErvitiJ Mark Cooper
May 5, 2011·Biochimica Et Biophysica Acta·Lisandro J Falomir-LockhartBetina Córsico
Jul 5, 2011·Traffic·S Brookhart Shields, Robert C Piper
Jul 13, 2011·The Journal of Cell Biology·Petranka KrumovaJochen H Weishaupt
Jul 19, 2011·Developmental Cell·William M HenneScott D Emr
Aug 5, 2011·Neurobiology of Aging·Anne-Laure MougenotThierry Baron

❮ Previous
Next ❯

Citations

Jul 28, 2015·Biomolecules·Shamini VijayakumaranDean L Pountney
Dec 23, 2015·Ageing Research Reviews·Nicoletta Plotegher, Luigi Bubacco
Mar 20, 2016·Cellular and Molecular Neurobiology·Robert C RennertBob S Carter
May 1, 2015·Journal of Proteome Research·Simion KreimerAlexander R Ivanov
Apr 20, 2016·Journal of Neurochemistry·Björn H FalkenburgerElisabeth Dinter
Mar 5, 2016·Brain Pathology·Evangelia Emmanouilidou, Kostas Vekrellis
May 21, 2016·Frontiers in Synaptic Neuroscience·Lenka Schorova, Stéphane Martin
Mar 5, 2016·Journal of Neurochemistry·Ana Cristina Guerra de SouzaHelena Cimarosti
Jun 30, 2016·The Journal of Cell Biology·Jingyi GongRüdiger Klein
Nov 25, 2016·Nature Communications·Carolina Villarroya-BeltriFrancisco Sánchez-Madrid
Jan 15, 2017·Molecular Neurodegeneration·Yipeng WangEva-Maria Mandelkow
Mar 2, 2017·International Journal of Cancer. Journal International Du Cancer·Colin MooreJameel M Inal
Nov 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ruth RottSimone Engelender
Aug 27, 2017·Journal of Cell Science·Carolina Villarroya-BeltriFrancisco Sánchez-Madrid
May 29, 2018·Journal of Neurochemistry·Matteo AudanoNico Mitro
Nov 21, 2018·Expert Review of Proteomics·Bethany ClaridgeDavid W Greening
Dec 12, 2018·The International Journal of Neuropsychopharmacology·Cristóbal Gómez-MolinaUrsula Wyneken
Nov 15, 2019·Current Pharmaceutical Design·Biancamaria LongoniRoberto Maggio
Sep 19, 2018·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Surbhi SharmaMartin R Schiller
Mar 24, 2020·Nature Reviews. Neurology·Chao PengVirginia M-Y Lee
Sep 7, 2019·Molecular Neurodegeneration·Anna MasatoLuigi Bubacco
Jan 31, 2017·Neural Plasticity·Francesca LonghenaArianna Bellucci
Jul 17, 2020·Frontiers in Aging Neuroscience·Mor Savyon, Simone Engelender
Nov 18, 2016·The Journal of Biological Chemistry·Jason Howitt, Andrew F Hill
Oct 26, 2016·International Journal of Oncology·Gabriella SchieraItalia Di Liegro
Oct 6, 2018·Cellular and Molecular Neurobiology·Björn H Falkenburger
Feb 8, 2019·Therapeutic Delivery·Hanin AlyamaniValerie A Ferro
Feb 20, 2020·Military Medicine·Alakesh BeraMeera Srivastava
Oct 9, 2019·Translational Psychiatry·Gaurav JainAndre Fischer
Oct 29, 2017·Cellular and Molecular Life Sciences : CMLS·Olga Moreno-GonzaloFrancisco Sanchez-Madrid
May 10, 2019·Journal of Neurochemistry·Leonidas StefanisGeorge K Tofaris
Aug 1, 2019·Cellular and Molecular Life Sciences : CMLS·Hiroshi Ageta, Kunihiro Tsuchida
Mar 21, 2019·International Journal of Molecular Sciences·Sabrina RoyBob S Carter
Jun 13, 2020·Frontiers in Immunology·Jonathan M CarninoYang Jin
Sep 9, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Benjamin DehayJeffrey H Kordower
Dec 28, 2016·Neuroscience Bulletin·Xiaoqing WuBaorong Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
sumoylation
the
PCR
transfection
fluorescence assay
column chromatography
electrophoresis
NMR
gel-filtration

Software Mentioned

Image J
MSD Discovery Workbench
Nanoparticle Tracking Analysis ( NTA )
Mathematica

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved