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Updated: Nov 10, 2025
07:56
Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
Published on: May 30, 2021
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ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization
Jianmin Si1, Chris Van den Haute1,2, Evy Lobbestael1
1Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Herestraat 49, Bus 1023, 3000 Leuven, Belgium.
International Journal of Molecular Sciences
|April 3, 2021
Summary
The ATP13A2 transporter impacts neurodegenerative diseases by affecting α-synuclein. Loss of ATP13A2 causes α-synuclein multimerization, while its overexpression protects against it, revealing dual roles in polyamine transport and α-synuclein regulation.
Area of Science:
- Neurobiology
- Cell Biology
- Molecular Medicine
Background:
- ATP13A2 is a lysosomal transporter linked to neurodegenerative diseases like Parkinson's.
- Mutations in ATP13A2 impair polyamine export, causing lysosomal dysfunction.
- ATP13A2's role in α-synuclein regulation remains unclear.
Purpose of the Study:
- To investigate the mechanisms linking ATP13A2 activity to α-synuclein behavior.
- To explore ATP13A2's function in cell models with altered transporter activity.
Main Methods:
- Utilized cell models with modified ATP13A2 expression (loss-of-function and overexpression).
- Assessed lysosomal integrity, α-synuclein multimerization, and membrane association.
- Investigated α-synuclein secretion via nanovesicles and polyubiquitination.
Main Results:
- Loss of ATP13A2 impairs lysosomal integrity and promotes α-synuclein multimerization, exacerbated by stress or spermine.
- ATP13A2 overexpression protects against α-synuclein multimerization and enhances its secretion via nanovesicles.
- ATP13A2 influences α-synuclein polyubiquitination and externalization through both transport-dependent and independent mechanisms.
Conclusions:
- ATP13A2 plays a critical role in maintaining lysosomal function and regulating α-synuclein.
- The transporter impacts α-synuclein multimerization, secretion, and ubiquitination.
- ATP13A2's functions extend beyond its ATPase and transport activity, influencing neurodegeneration pathways.
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