Chaperone Mediated Autophagy Degrades TDP-43 Protein and Is Affected by TDP-43 Aggregation

Frontiers in Molecular Neuroscience
Fernando OrmeñoMauricio Budini

Abstract

TAR DNA binding protein 43 kDa (TDP-43) is a ribonuclear protein regulating many aspects of RNA metabolism. Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) are fatal neurodegenerative diseases with the presence of TDP-43 aggregates in neuronal cells. Chaperone Mediated Autophagy (CMA) is a lysosomal degradation pathway participating in the proteostasis of several cytosolic proteins including neurodegenerative associated proteins. In addition, protein oligomers or aggregates can affect the status of CMA. In this work, we studied the relationship between CMA and the physiological and pathological forms of TDP-43. First, we found that recombinant TDP-43 was specifically degraded by rat liver's CMA+ lysosomes and that endogenous TDP-43 is localized in rat brain's CMA+ lysosomes, indicating that TDP-43 can be a CMA substrate in vivo. Next, by using a previously reported TDP-43 aggregation model, we have shown that wild-type and an aggregate-prone form of TDP-43 are detected in CMA+ lysosomes isolated from cell cultures. In addition, their protein levels increased in cells displaying CMA down-regulation, indicating that these two TDP-43 forms are CMA substrates in vitro. Finally, we observed that the ...Continue Reading

References

Jan 1, 1990·Methods in Enzymology·B Storrie, E A Madden
Aug 1, 1990·Trends in Biochemical Sciences·J F Dice
Nov 1, 1995·The American Journal of Physiology·A M CuervoJ F Dice
May 19, 1997·The Journal of Cell Biology·F A AgarraberesJ F Dice
Feb 24, 2001·Traffic·A M Cuervo, J F Dice
Jan 11, 2007·Journal of Microscopy·S Bolte, F P Cordelières
Apr 4, 2007·Autophagy·J Fred Dice
Apr 22, 2008·Methods in Molecular Biology·S Kaushik, A M Cuervo
Jun 21, 2008·The Journal of Biological Chemistry·Tereza VogiatziLeonidas Stefanis
Oct 18, 2008·Autophagy·Urmi Bandyopadhyay, Ana Maria Cuervo
Feb 10, 2009·Methods in Enzymology·Susmita Kaushik, Ana Maria Cuervo
Feb 21, 2009·The EMBO Journal·Martin GamerdingerChristian Behl
Aug 6, 2009·Human Molecular Genetics·Yipeng WangEckhard Mandelkow
Sep 10, 2009·Advances in Genetics·Emanuele Buratti, Francisco E Baralle
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
Nov 26, 2010·Current Opinion in Cell Biology·Esperanza Arias, Ana Maria Cuervo
Jan 18, 2011·Developmental Cell·Ranjit SahuLaura Santambrogio
Jul 14, 2011·Nature Communications·Hiroshi KogaAna Maria Cuervo
Dec 1, 2011·Nature Reviews. Neuroscience·Edward B LeeJohn Q Trojanowski
Dec 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hiroshi KogaAna Maria Cuervo
Jan 12, 2012·The Journal of Biological Chemistry·Mauricio BudiniFrancisco E Baralle
Apr 27, 2012·Trends in Biochemical Sciences·Emanuele Buratti, Francisco E Baralle
Oct 17, 2012·PloS One·Lin QiZheng-Hong Qin
Mar 5, 2013·Nature Neuroscience·Samantha J OrensteinAna Maria Cuervo
Nov 10, 2013·Nature Reviews. Molecular Cell Biology·Christopher A LambSharon A Tooze
Nov 22, 2013·Biochemical Society Transactions·Jaime L Schneider, Ana Maria Cuervo
Dec 21, 2013·Trends in Molecular Medicine·Lies Vanden BroeckBart Dermaut
May 27, 2014·Journal of Cell Science·Chi-Chen HuangChe-Kun James Shen
Jan 18, 2015·Methods : a Companion to Methods in Enzymology·Bindi Patel, Ana Maria Cuervo
Jan 27, 2015·Aging Cell·Jaime L SchneiderAna Maria Cuervo
Jan 16, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Nikolaos PapagiannakisLeonidas Stefanis
Mar 16, 2016·The Journal of Cell Biology·Danielle E JohnsonSergio Grinstein

❮ Previous
Next ❯

Citations

Aug 15, 2020·Frontiers in Aging Neuroscience·Riccardo CristofaniAngelo Poletti
Dec 2, 2020·Journal of Neurochemistry·Weilun Pang, Fenghua Hu
Jan 4, 2021·Molecular and Cellular Biochemistry·Zhaozhong LiaoNing Li
Nov 3, 2020·Frontiers in Aging Neuroscience·Jessica TittelmeierCarmen Nussbaum-Krammer
Feb 27, 2021·Frontiers in Aging Neuroscience·Jaione Auzmendi-Iriarte, Ander Matheu
May 13, 2021·PeerJ·Zhi Xiong ChongWan Yong Ho
Jul 3, 2021·International Journal of Molecular Sciences·Han-Jou Chen, Jacqueline C Mitchell

❮ Previous
Next ❯

Methods Mentioned

BETA
transfections
immunoprecipitation

Software Mentioned

ImageJ
Fiji
GraphPad

Related Concepts

Related Feeds

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Tetsuaki Arai
Acta Neuropathologica Communications
Rui LiuMax S Cynader
Brain and nerve = Shinkei kenkyū no shinpo
Takashi NonakaMasato Hasegawa
© 2021 Meta ULC. All rights reserved