Presynaptic Alpha(2)Delta-3 Is Required For Synaptic Morphogenesis Independent Of Its Ca2+-Channel Functions

Synaptogenesis involves the transformation of a growth cone into synaptic boutons specialized for transmitter release. In Drosophila embryos lacking the. alpha(2)delta-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 alpha(2)delta-3 protein has been thought to function strictly as an auxiliary subunit of the Ca2+ channel, but the phenotype of alpha(2)delta-3 (also known as stj) mutations cannot be explained by a channel defect; embryos lacking the pore-forming alpha(1) subunit cacophony formed boutons. The synaptogenic function of. alpha(2)delta-3 required only the alpha(2) peptide, whose expression sufficed to rescue bouton formation. Our results indicate that alpha(2)delta 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.