MDGAs as synaptic suppressors with implications in neurodevelopmental disorders

Abstract

The MDGA family proteins, MDGA1 and MDGA2, are glycophosphatidylinositol (GPI)-anchored proteins with high expression in the central nervous system. Initially associated with neuronal migration, MDGAs also act as synaptic suppressors in postsynaptic neurons, where they interfere with functions of key synapse organizing proteins. Strikingly, the MDGAs act upon distinct extracellular binding proteins to negatively control different synaptic properties of diverse synapses and neural circuits. This review discusses recent research on MDGAs and highlights debates and unresolved questions to invigorate future research activities aimed at determining precisely how MDGAs modulate synaptic properties in the context of neural circuits. Given that MDGAs and their interacting proteins are strongly linked with various neurodevelopmental disorders, understanding how synaptic signaling pathways encompassing MDGA protein complexes will be instrumental for better understanding the pathophysiological mechanisms of associated brain disorders.