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Monomeric α-Synuclein activates the Plasma Membrane Calcium Pump [article]

Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Montana Caballero Bermejo, Poul Henning Jensen, Poul Nissen
2022 bioRxiv   pre-print

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https://web.archive.org/web/20220424070826/https://www.biorxiv.org/content/biorxiv/early/2022/02/22/2022.02.21.481193.full.pdf

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Alpha-synuclein (aSN) is a membrane-associated and intrinsically disordered protein, well-known for pathological aggregation in neurodegeneration. The physiological function of aSN however is disputed. Pull-down experiments have pointed to plasma membrane Ca2+-ATPase (PMCA) as a potential interaction partner. From proximity ligation assays we find here that aSN and PMCA colocalize at neuronal synapses, and that calcium expulsion is activated by aSN and PMCA. From PMCA activity studies we show
more » ... at soluble, monomeric aSN activates PMCA at par with calmodulin, yet independent of the autoinhibitory domain of PMCA, but highly dependent on acidic phospholipids and the membrane-anchoring N-terminus of aSN. On the PMCA molecule, the interaction site is mapped to the acidic lipid-binding site, located within a PMCA-specific linker region connecting the cytosolic A domain and transmembrane segment 3. Our studies point towards a physiological role of monomeric aSN as a stimulator of calcium clearance in neurons through activation of PMCA
doi:10.1101/2022.02.21.481193 fatcat:6hlgs6svvbeyxdkk526hoend7q
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Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Montana Caballero Bermejo, Poul Henning Jensen, Poul Nissen. "Monomeric α-Synuclein activates the Plasma Membrane Calcium Pump." bioRxiv (2022)