Deciphering the role of specific membrane transporters in extracellular vesicles

Solute carrier proteins (SLCs) are a vast superfamily of membrane proteins found on organelles and the plasma membrane of cells. Their role is to regulate the flux of a big variety of molecules across membranes and therefore modulate cellular homeostasis and function. In neurons, SLCs influence gene regulation, metabolic functions, and synaptic properties. Indeed, current research indicates that they play a pivotal role in several diseases.Previous published proteomic analyses show that several SLCs are frequently found in the membrane of extracellular vesicles (EVs) obtained from different biological sources, raising the possibility that they play an important role in modulating EVs content and function. EVs are membranous structures secreted by cells known to mediate several biological processes in recipient cells. In the brain, EVs were shown to impact structural and synaptic properties of target cells as well as mediate key aspects of disease.By employing constitutive and conditional knockout mouse models and human cerebral organoids from patient-derived induced-pluripotent stem cells, we aim to decipher specific roles of SLCs in EVs in both physiological and disease-related conditions. Furthermore, by delivering EVs in vivo to mutant mice and characterizing their effects, we aim to assess the therapeutic potential of SLC-containing EVs in the context of neurodevelopmental disorders.