Autism spectrum disorders (ASD) affect approximately 1% of the population worldwide. They are predominantly associated with genetic factors. Genetic variants of voltage-gated calcium channel (VGCC) subunits have also been associated with ASD. A pathophysiological significance sounds plausible since VGCC is essential for electrical activity, morphology, transmitter release, and gene transcription of neurons. We have shown that mutations of VGCC β-helper subunits (CaVβ) identified in the genome of affected individuals lead to altered calcium currents in the cell membrane.
While an increase in VGCC activity appears to be a common feature of mutant CaVβ2 isoforms, recent findings suggest an inhibitory effect of mutant CaVβ1 auxiliary subunits. Research on the importance of CaVβ variants for ASD is still in its early stages. The next steps include studies on the impact on neuronal cell morphology and function and characterization of protein-protein interactions with intracellular interaction partners.
For further information, please get in touch with Priv.-Doz. Dr. Jan Matthes.
