Presynaptic α <sub>2</sub> δ subunits are key organizers of glutamatergic synapses
Clemens L. Schöpf, Cornelia Ablinger, Stefanie M. Geisler, Ruslan I. Stanika, Marta Campiglio, Walter A. Kaufmann, Benedikt Nimmervoll, Bettina Schlick, Johannes Brockhaus, Markus Missler, Ryuichi Shigemoto, Gerald J. Obermair
Abstract
Significance Voltage-gated calcium channels are important regulators of neuronal functions, as for example synaptic transmission. Their auxiliary α 2 δ subunits are modulating the calcium currents. Beyond that they have emerged as modulators of synaptic functions. Here, we established a cellular triple knockout/knockdown model in cultured hippocampal neurons by knocking out or knocking down the expression of all three α 2 δ subunits expressed in brain. Our experiments demonstrate that the presynaptic loss of α 2 δ proteins leads to a severe defect in glutamatergic synapse formation, which could be rescued by reintroducing any of the three neuronal α 2 δ isoforms. Thus, our study suggests that α 2 δ proteins are critical regulators of excitatory synapse formation and thereby contributes to the understanding of basic nerve cell functions.