LC3/GABARAP binding to fluid membranes is potentiated by ceramide.

Yaiza R Varela, Alicia Alonso

Autophagy 2023 Apr

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LC3/GABARAP constitute a macroautophagy/autophagy-related protein family derived from yeast Atg8. The involvement of specific lipids in LC3/GABARAP function is poorly understood. Exploring the interaction of LC3/GABARAP proteins with phosphatidylcholine- or sphingomyelin-based bilayers has revealed that cardiolipin is essential for the protein-bilayer interaction, and that ceramide markedly increases binding. Giant unilamellar vesicles examined under confocal fluorescence microscopy reveal that ceramide segregates laterally into very rigid domains, while GABARAP binds only the more fluid regions, suggesting that the enhancing role of ceramide is exerted by the minority of ceramide molecules dispersed in the fluid phase.Abbreviations: Atg8: autophagy-related 8; Cer: ceramide; CL: cardiolipin; eCer: egg ceramide; GABARAP: gamma-aminobutyric acid receptor associated protein; GUV: giant unilamellar vesicle; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Rho-PE: lissamine rhodamine phosphatidylethanolamine; SM: sphingomyelin.