Erythrocytes have a remarkable ability to deform. This deformability depends on a dynamic cytoskeleton but also on surface lipid domains involved in membrane deformation and calcium exchanges. In this work, we investigated whether and how lipid domains are altered and contribute to the pathophysiology of hereditary elliptocytosis and spherocytosis, two erythrocytes diseases caused by cytoskeletal defects. Our results show impairment of the abundance, properties and functionality of the domains involved in calcium exchange. Depending on the disease and its severity, those alterations are accompanied by an overactivation of the plasmatic acid sphingomyelinase, an increase in the intracellular calcium content and an activation of downstream signaling pathways, resulting into impaired membrane asymmetry and increased oxidative stress. This study paves the way towards a better understanding of the molecular mechanisms behind both diseases and opens new perspectives for treatment.
Affiliations
UCLouvainSSS/DDUV - Institut de Duve
Citations
APA
Chicago
FWB
Pollet, H. (2019). How cytoskeletal impairment in hereditary elliptocytosis and spherocytosis affects erythrocyte membrane composition, organization and deformation. https://hdl.handle.net/2078.5/127364