Monomeric α-synuclein activates the plasma membrane calcium pump
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 3.13 MB, PDF document
Alpha-synuclein (aSN) is a membrane-associated and intrinsically disordered protein, well known for pathological aggregation in neurodegeneration. However, the physiological function of aSN is disputed. Pull-down experiments have pointed to plasma membrane Ca2+-ATPase (PMCA) as a potential interaction partner. From proximity ligation assays, we find that aSN and PMCA colocalize at neuronal synapses, and we show that calcium expulsion is activated by aSN and PMCA. We further show that soluble, monomeric aSN activates PMCA at par with calmodulin, but independent of the autoinhibitory domain of PMCA, and highly dependent on acidic phospholipids and membrane-anchoring properties of aSN. On PMCA, the key site is mapped to the acidic lipid-binding site, located within a disordered PMCA-specific loop connecting the cytosolic A domain and transmembrane segment 3. Our studies point toward a novel physiological role of monomeric aSN as a stimulator of calcium clearance in neurons through activation of PMCA.
Original language | English |
---|---|
Article number | e111122 |
Journal | EMBO Journal |
Volume | 42 |
Issue number | 23 |
Number of pages | 21 |
ISSN | 0261-4189 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
- alpha-synuclein, calcium, calmodulin, plasma membrane Ca-ATPase, presynapse
Research areas
ID: 372813949