Monomeric α-synuclein activates the plasma membrane calcium pump

Research output: Contribution to journal › Journal article › Research › peer-review

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Monomeric α-synuclein activates the plasma membrane calcium pump. / Kowalski, Antoni; Betzer, Cristine; Larsen, Sigrid Thirup; Gregersen, Emil; Newcombe, Estella A.; Bermejo, Montaña Caballero; Bendtsen, Viktor Wisniewski; Diemer, Jorin; Ernstsen, Christina V.; Jain, Shweta; Bou, Alicia Espiña; Langkilde, Annette Eva; Nejsum, Lene N.; Klipp, Edda; Edwards, Robert; Kragelund, Birthe B.; Jensen, Poul Henning; Nissen, Poul.

In: EMBO Journal, Vol. 42, No. 23, e111122, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kowalski, A, Betzer, C, Larsen, ST, Gregersen, E, Newcombe, EA, Bermejo, MC, Bendtsen, VW, Diemer, J, Ernstsen, CV, Jain, S, Bou, AE, Langkilde, AE, Nejsum, LN, Klipp, E, Edwards, R, Kragelund, BB, Jensen, PH & Nissen, P 2023, 'Monomeric α-synuclein activates the plasma membrane calcium pump', EMBO Journal, vol. 42, no. 23, e111122. https://doi.org/10.15252/embj.2022111122

APA

Kowalski, A., Betzer, C., Larsen, S. T., Gregersen, E., Newcombe, E. A., Bermejo, M. C., Bendtsen, V. W., Diemer, J., Ernstsen, C. V., Jain, S., Bou, A. E., Langkilde, A. E., Nejsum, L. N., Klipp, E., Edwards, R., Kragelund, B. B., Jensen, P. H., & Nissen, P. (2023). Monomeric α-synuclein activates the plasma membrane calcium pump. EMBO Journal, 42(23), [e111122]. https://doi.org/10.15252/embj.2022111122

Vancouver

Kowalski A, Betzer C, Larsen ST, Gregersen E, Newcombe EA, Bermejo MC et al. Monomeric α-synuclein activates the plasma membrane calcium pump. EMBO Journal. 2023;42(23). e111122. https://doi.org/10.15252/embj.2022111122

Author

Kowalski, Antoni ; Betzer, Cristine ; Larsen, Sigrid Thirup ; Gregersen, Emil ; Newcombe, Estella A. ; Bermejo, Montaña Caballero ; Bendtsen, Viktor Wisniewski ; Diemer, Jorin ; Ernstsen, Christina V. ; Jain, Shweta ; Bou, Alicia Espiña ; Langkilde, Annette Eva ; Nejsum, Lene N. ; Klipp, Edda ; Edwards, Robert ; Kragelund, Birthe B. ; Jensen, Poul Henning ; Nissen, Poul. / Monomeric α-synuclein activates the plasma membrane calcium pump. In: EMBO Journal. 2023 ; Vol. 42, No. 23.

Bibtex

@article{5901f5d0bb414056a17e1bb41c13b535,

title = "Monomeric α-synuclein activates the plasma membrane calcium pump",

abstract = "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.",

keywords = "alpha-synuclein, calcium, calmodulin, plasma membrane Ca-ATPase, presynapse",

author = "Antoni Kowalski and Cristine Betzer and Larsen, {Sigrid Thirup} and Emil Gregersen and Newcombe, {Estella A.} and Bermejo, {Monta{\~n}a Caballero} and Bendtsen, {Viktor Wisniewski} and Jorin Diemer and Ernstsen, {Christina V.} and Shweta Jain and Bou, {Alicia Espi{\~n}a} and Langkilde, {Annette Eva} and Nejsum, {Lene N.} and Edda Klipp and Robert Edwards and Kragelund, {Birthe B.} and Jensen, {Poul Henning} and Poul Nissen",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY 4.0 license.",

year = "2023",

doi = "10.15252/embj.2022111122",

language = "English",

volume = "42",

journal = "E M B O Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

number = "23",

}

RIS

TY - JOUR

T1 - Monomeric α-synuclein activates the plasma membrane calcium pump

AU - Kowalski, Antoni

AU - Betzer, Cristine

AU - Larsen, Sigrid Thirup

AU - Gregersen, Emil

AU - Newcombe, Estella A.

AU - Bermejo, Montaña Caballero

AU - Bendtsen, Viktor Wisniewski

AU - Diemer, Jorin

AU - Ernstsen, Christina V.

AU - Jain, Shweta

AU - Bou, Alicia Espiña

AU - Langkilde, Annette Eva

AU - Nejsum, Lene N.

AU - Klipp, Edda

AU - Edwards, Robert

AU - Kragelund, Birthe B.

AU - Jensen, Poul Henning

AU - Nissen, Poul

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - alpha-synuclein

KW - calcium

KW - calmodulin

KW - plasma membrane Ca-ATPase

KW - presynapse

U2 - 10.15252/embj.2022111122

DO - 10.15252/embj.2022111122

M3 - Journal article

C2 - 37916890

AN - SCOPUS:85175703796

VL - 42

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 23

M1 - e111122

ER -

ID: 372813949

Department of Biology