A negative regulator of synaptic development: MDGA and its links to neurodevelopmental disorders

Formation of protein complexes across synapses is a critical process in neurodevelopment, having direct implications on brain function and animal behavior. Here, we present the understanding, importance, and potential impact of a newly found regulator of such a key interaction.

A systematic search of the literature was conducted on PubMed (Medline), Embase, and Central-Cochrane Database.

Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) were recently discovered to regulate synaptic development and transmission via suppression of neurexins-neuroligins trans-synaptic complex formation. MDGAs also regulate axonal migration and outgrowth. In the context of their physiological role, we begin to consider the potential links to the etiology of certain neurodevelopmental disorders. We present the gene expression and protein structure of MDGAs and discuss recent progress in our understanding of the neurobiological role of MDGAs to explore its potential as a therapeutic target.

MDGAs play a key role in neuron migration, axon guidance and synapse development, as well as in regulating brain excitation and inhibition balance.