Speaker Details

Speaker GO


α2δ mutations linked to brain disorders affect synaptic functions

α2δ proteins serve as auxiliary subunits of voltage-gated calcium channels, which are essential components of excitable cells such as nerve and muscle cells. Over the recent years, α2δ proteins have been identified as critical regulators of synaptic functions. Moreover, the genes encoding for the four α2δ isoforms have been linked to neurological and neurodevelopmental disorders including epilepsy, autism spectrum disorders, schizophrenia, and depressive and bipolar disorders. Despite the increasing number of potentially disease-associated mutations, the underlying pathophysiological mechanisms are only beginning to emerge. Using heterologous and homologous expression and analyses of specific knockout and mutant mouse models, we show that mutated α2δ proteins can alter synaptic functions, both, via their role as calcium channel subunits and as independent regulatory entities.