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

Ward, Katherine E.; Sengupta, Ranjan; Ropa, James P.; Amiar, Souad; Stahelin, Robert V.

doi:10.3390/biom10040647

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

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

¹,

^1,†

and

^2,3,*

Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46556, USA

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47906, USA

Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA

Author to whom correspondence should be addressed.

^†

Current address: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Biomolecules 2020, 10(4), 647; https://doi.org/10.3390/biom10040647

Received: 11 March 2020 / Revised: 16 April 2020 / Accepted: 19 April 2020 / Published: 22 April 2020

(This article belongs to the Special Issue 2020 Feature Papers by Biomolecules’ Editorial Board Members)

View Full-Text Download PDF

Browse Figures

Citation Export

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 investigated 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 showed that cPLA₂α undergoes C2 domain-dependent oligomerization on membranes in vitro and in 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 localizes to cholesterol enriched Golgi-derived vesicles independently of cPLA₂α catalytic activity. Moreover, we demonstrate the C2 domain selectively localizes to lipid droplets whereas the full-length enzyme to a much lesser extent. Our results therefore provide novel insight into the molecular forces that mediate C2 domain-dependent membrane localization in vitro and in cells. View Full-Text

Keywords: cytosolic phospholipase A₂α (cPLA₂α); electron microscopy; Golgi; membrane bending; membrane curvature; C2 domain; oligomerization

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Share and Cite

MDPI and ACS Style

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. https://doi.org/10.3390/biom10040647

AMA Style

Ward KE, Sengupta R, Ropa JP, Amiar S, Stahelin RV. The Cytosolic Phospholipase A₂α N-Terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature. Biomolecules. 2020; 10(4):647. https://doi.org/10.3390/biom10040647

Chicago/Turabian Style

Ward, Katherine E., Ranjan Sengupta, James P. Ropa, Souad Amiar, and Robert V. Stahelin 2020. "The Cytosolic Phospholipase A₂α N-Terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature" Biomolecules 10, no. 4: 647. https://doi.org/10.3390/biom10040647

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI