Membrane curvature induced by proximity of anionic phospholipids can initiate endocytosis

Takashi Hirama; Stella M. Lu; Jason G. Kay; Masashi Maekawa; Michael M. Kozlov; Sergio Grinstein; Gregory D. Fairn

doi:10.1038/s41467-017-01554-9

Membrane curvature induced by proximity of anionic phospholipids can initiate endocytosis

Takashi Hirama, Stella M. Lu, Jason G. Kay, Masashi Maekawa, Michael M. Kozlov, Sergio Grinstein, Gregory D. Fairn

Research output: Contribution to journal › Article › peer-review

79 Citations (Scopus)

Abstract

The plasma membrane is uniquely enriched in phosphatidylserine (PtdSer). This anionic phospholipid is restricted almost exclusively to the inner leaflet of the plasmalemma. Because of their high density, the headgroups of anionic lipids experience electrostatic repulsion that, being exerted asymmetrically, is predicted to favor membrane curvature. We demonstrate that cholesterol limits this repulsion and tendency to curve. Removal of cholesterol or insertion of excess PtdSer increases the charge density of the inner leaflet, generating foci of enhanced charge and curvature where endophilin and synaptojanin are recruited. From these sites emerge tubules that undergo fragmentation, resulting in marked endocytosis of PtdSer. Shielding or reduction of the surface charge or imposition of outward membrane tension minimized invagination and PtdSer endocytosis. We propose that cholesterol associates with PtdSer to form nanodomains where the headgroups of PtdSer are maintained sufficiently separated to limit spontaneous curvature while sheltering the hydrophobic sterol from the aqueous medium.

Original language	English
Article number	1393
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01554-9
Publication status	Published - Dec 1 2017
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by an Operating Grants MOP-133656 and a Foundation Grant FDN-143202 from the Canadian Institutes of Health Research (CIHR) to G.D.F and S.G., respectively. G.D.F. is also a recipient of a New Investigator Award from the CIHR and an Early Researcher Award from the Government of Ontario. The authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

Publisher Copyright:
© 2017 The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Cite this

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abstract = "The plasma membrane is uniquely enriched in phosphatidylserine (PtdSer). This anionic phospholipid is restricted almost exclusively to the inner leaflet of the plasmalemma. Because of their high density, the headgroups of anionic lipids experience electrostatic repulsion that, being exerted asymmetrically, is predicted to favor membrane curvature. We demonstrate that cholesterol limits this repulsion and tendency to curve. Removal of cholesterol or insertion of excess PtdSer increases the charge density of the inner leaflet, generating foci of enhanced charge and curvature where endophilin and synaptojanin are recruited. From these sites emerge tubules that undergo fragmentation, resulting in marked endocytosis of PtdSer. Shielding or reduction of the surface charge or imposition of outward membrane tension minimized invagination and PtdSer endocytosis. We propose that cholesterol associates with PtdSer to form nanodomains where the headgroups of PtdSer are maintained sufficiently separated to limit spontaneous curvature while sheltering the hydrophobic sterol from the aqueous medium.",

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Membrane curvature induced by proximity of anionic phospholipids can initiate endocytosis

Abstract

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