dc.contributor.author |
Jacob, Reeba Susan |
|
dc.contributor.author |
Eichmann, Cédric |
|
dc.contributor.author |
Dema, Alessandro |
|
dc.contributor.author |
Mercadante, Davide |
|
dc.contributor.author |
Selenko, Philipp |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2022-02-03T20:07:00Z |
|
dc.date.available |
2022-02-03T20:07:00Z |
|
dc.date.issued |
2021-2-15 |
|
dc.identifier.citation |
eLife, 10, 15 Feb 2021 |
|
dc.identifier.issn |
2050-084X |
|
dc.identifier.uri |
https://hdl.handle.net/2292/58115 |
|
dc.description.abstract |
The Parkinson's disease protein α-synuclein (αSyn) promotes membrane fusion and fission by interacting with various negatively charged phospholipids. Despite postulated roles in endocytosis and exocytosis, plasma membrane (PM) interactions of αSyn are poorly understood. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) and phosphatidylinositol 3,4,5-trisphosphate (PIP<sub>3</sub>), two highly acidic components of inner PM leaflets, mediate PM localization of endogenous pools of αSyn in A2780, HeLa, SK-MEL-2, and differentiated and undifferentiated neuronal SH-SY5Y cells. We demonstrate that αSyn binds to reconstituted PIP<sub>2</sub> membranes in a helical conformation in vitro and that PIP<sub>2</sub> synthesizing kinases and hydrolyzing phosphatases reversibly redistribute αSyn in cells. We further delineate that αSyn-PM targeting follows phosphoinositide-3 kinase (PI3K)-dependent changes of cellular PIP<sub>2</sub> and PIP<sub>3</sub> levels, which collectively suggests that phosphatidylinositol polyphosphates contribute to αSyn's function(s) at the plasma membrane. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
eLife Sciences Publications, Ltd |
|
dc.relation.ispartofseries |
eLife |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
A2780 |
|
dc.subject |
HeLa |
|
dc.subject |
SH-SY5Y |
|
dc.subject |
SK-MEL-2 |
|
dc.subject |
human cell lines |
|
dc.subject |
neuroscience |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Biology |
|
dc.subject |
Life Sciences & Biomedicine - Other Topics |
|
dc.subject |
PLECKSTRIN HOMOLOGY DOMAINS |
|
dc.subject |
BINDING |
|
dc.subject |
CURVATURE |
|
dc.subject |
RECEPTOR |
|
dc.subject |
PHOSPHOINOSITIDES |
|
dc.subject |
ACTIVATION |
|
dc.subject |
MULTIPLE |
|
dc.subject |
PHOSPHOLIPIDS |
|
dc.subject |
DETERMINANTS |
|
dc.subject |
ORGANIZATION |
|
dc.subject |
0601 Biochemistry and Cell Biology |
|
dc.title |
α-Synuclein plasma membrane localization correlates with cellular phosphatidylinositol polyphosphate levels. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.7554/elife.61951 |
|
pubs.begin-page |
e61951 |
|
pubs.volume |
10 |
|
dc.date.updated |
2022-01-10T22:24:56Z |
|
dc.rights.holder |
Copyright: The authors |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/33587036 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
842249 |
|
dc.identifier.eissn |
2050-084X |
|
dc.identifier.pii |
61951 |
|
pubs.number |
ARTN e61951 |
|
pubs.online-publication-date |
2021-2-15 |
|