Biogenesis and transport of membrane domains-potential implications in brain pathologies

Abstract

Lipids in biological membranes show astonishing chemical diversity, but they also show some key conserved structures in different organisms. In addition, some of their biophysical properties have been related to specific functions. In this review, we aim to discuss the role of sphingolipids- and cholesterol-rich micro- and nano-membrane domains (MD) and highlight their pivotal role in lipid-protein clustering processes, vesicle biogenesis and membrane fusion. We further review potential connections between human pathologies and defects in MD biosynthesis, recycling and homeostasis. Brain, which is second only to the adipose tissues in term of lipid abundance, is particularly affected by MD defects which are linked to neurodegenerative disorders. Finally we propose a potential connection between MD and several nutrient-related processes and envision how diet and autophagy could bring insights towards understanding the impact of global lipid homeostasis on human health and disease.

Keywords: DRM; EGFR; G protein coupled receptor; GPCR; GPI; GUV; MD; Membrane domains; PMA1; SNAREs; TGN; VLCFA; VSVG; Very long chain fatty acid; detergent resistant membrane; epidermal growth factor receptor; giant unilamellar vesicle; glycosylphosphatidylinositol; membrane domains; plasma membrane ATPase 1; soluble N-ethylmaleimide sensitive factor attachment protein receptors; trans Golgi network; very long chain fatty acid; viral G glycoprotein of the vesicular stomatitis virus.