Presynaptic α2δ-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions

Publisher Website
Google Scholar
Abstract
The main function of the α2δ-3 calcium channel subunit is thought to be facilitation of the pore-forming subunit delivery to presynaptic terminals. Kurshan et al. now show that this subunit has other, independent synaptogenic functions and that it is important for shaping the architecture of the synapse. Synaptogenesis involves the transformation of a growth cone into synaptic boutons specialized for transmitter release. In Drosophila embryos lacking the α2δ-3 subunit of presynaptic, voltage-dependent Ca2+ channels, we found that motor neuron terminals failed to develop synaptic boutons and cytoskeletal abnormalities arose, including the loss of ankyrin2. Nevertheless, functional presynaptic specializations were present and apposed to clusters of postsynaptic glutamate receptors. The α2δ-3 protein has been thought to function strictly as an auxiliary subunit of the Ca2+ channel, but the phenotype of α2δ-3 (also known as stj) mutations cannot be explained by a channel defect; embryos lacking the pore-forming α1 subunit cacophony formed boutons. The synaptogenic function of α2δ-3 required only the α2 peptide, whose expression sufficed to rescue bouton formation. Our results indicate that α2δ proteins have functions that are independent of their roles in the biophysics and localization of Ca2+ channels and that synaptic architecture depends on these functions.