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Elife. 2018 Mar 15;7. pii: e34394. doi: 10.7554/eLife.34394.

Acyl chain asymmetry and polyunsaturation of brain phospholipids facilitate membrane vesiculation without leakage.

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Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur et CNRS, Valbonne, France.
Instituto Biofisika (UPV/EHU, CSIC), Leioa, Spain.
Centre Commun de Microscopie Appliquée, Université Côte d'Azur, Nice, France.


Phospholipid membranes form cellular barriers but need to be flexible enough to divide by fission. Phospholipids generally contain a saturated fatty acid (FA) at position sn1 whereas the sn2-FA is saturated, monounsaturated or polyunsaturated. Our understanding of the impact of phospholipid unsaturation on membrane flexibility and fission is fragmentary. Here, we provide a comprehensive view of the effects of the FA profile of phospholipids on membrane vesiculation by dynamin and endophilin. Coupled to simulations, this analysis indicates that: (i) phospholipids with two polyunsaturated FAs make membranes prone to vesiculation but highly permeable; (ii) asymmetric sn1-saturated-sn2-polyunsaturated phospholipids provide a tradeoff between efficient membrane vesiculation and low membrane permeability; (iii) When incorporated into phospholipids, docosahexaenoic acid (DHA; omega-3) makes membranes more deformable than arachidonic acid (omega-6). These results suggest an explanation for the abundance of sn1-saturated-sn2-DHA phospholipids in synaptic membranes and for the importance of the omega-6/omega-3 ratio on neuronal functions.


Dynamin; bar domain; biochemistry; chemical biology; dynamin; membrane curvature; membrane deformation; membrane fission; membrane permeability; molecular biophysics; omega-3; omega-3 omega-6 PUFAs; omega-6; polyunsaturated phospholipid; structural biology

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