Working Paper Article Version 1 This version is not peer-reviewed

The Cytosolic Phospholipase A2α N-Terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature

Version 1 : Received: 11 March 2020 / Approved: 12 March 2020 / Online: 12 March 2020 (04:10:52 CET)

A peer-reviewed article of this Preprint also exists.

Ward, K.E.; Sengupta, R.; Ropa, J.P.; Amiar, S.; Stahelin, R.V. The Cytosolic Phospholipase A2α N-terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature. Biomolecules 2020, 10, 647. Ward, K.E.; Sengupta, R.; Ropa, J.P.; Amiar, S.; Stahelin, R.V. The Cytosolic Phospholipase A2α N-terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature. Biomolecules 2020, 10, 647.

Journal reference: Biomolecules 2020, 10, 647
DOI: 10.3390/biom10040647

Abstract

Group IV phospholipase A2α (cPLA2α) regulates the production of prostaglandins and leukotrienes via the formation of arachidonic acid from membrane phospholipids. The targeting and membrane binding of cPLA2α to the Golgi involves the N-terminal C2 domain whereas the catalytic domain produces arachidonic acid. Although most studies of cPLA2α concern its catalytic activity, it is also linked to homeostatic processes involving the generation of vesicles that traffic material from the Golgi to the plasma membrane. Here we investigate how membrane curvature influences the homeostatic role of cPLA2α in vesicular trafficking. The cPLA2α C2 domain is known to induce changes in positive membrane curvature, a process which is dependent on cPLA2α membrane penetration. We show that cPLA2α undergoes C2 domain-dependent oligomerization on membranes in vitro and in A549 cells. We found that the association of the cPLA2α C2 domain with membranes is limited to membranes with positive curvature, and enhanced C2 domain oligomerization was observed on vesicles ~50 nm in diameter. We demonstrated that the cPLA2α C2 domain generates cholesterol enriched Golgi-derived vesicles independently of cPLA2α catalytic activity. Our results therefore provide novel insight into the molecular forces that mediate C2 domain-dependent membrane localization in vitro and in cells.

Subject Areas

cytosolic phospholipase A2; electron microscopy; C2 domain; Golgi; membrane bending; membrane curvature; oligomerization

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