The morphological transition of growth cones to synaptic boutons characterizes synaptogenesis. Here we have isolated mutations in immaculate connections (imac; CG8566), a previously uncharacterized Drosophila gene encoding a member of the Kinesin-3 family. Whereas earlier studies in Drosophila implicated Kinesin-1 in transporting synaptic vesicle precursors, we find that Imac is essential for this transport. An unexpected feature of imac mutants is the failure of synaptic boutons to form. Motor neurons lacking imac properly target to muscles but remain within target fields as thin processes, a structure that is distinct from either growth cones or mature terminals. Few active zones form at these endings. We show that the arrest of synaptogenesis is not a secondary consequence of the absence of transmission. Our data thus indicate that Imac transports components required for synaptic maturation and provide insight into presynaptic maturation as a process that can be differentiated from axon outgrowth and targeting.
Synaptogenesis involves the transformation of a growth cone into synaptic boutons specialized for transmitter release. In Drosophila embryos lacking the α 2 δ-3 subunit of presynaptic, voltagedependent Ca 2+ channels, we find that motor neuron terminals fail to develop synaptic boutons and cytoskeletal abnormalities arise, including the loss of ankyrin2. Nevertheless, functional presynaptic specializations are present and apposed to clusters of postsynaptic glutamate receptors. Heretofore, the α 2 δ-3 protein has been thought to function strictly as an auxiliary subunit of the Ca 2+ channel, but the phenotype of α 2 δ-3 mutations cannot be explained by a channel defect: embryos lacking the pore-forming α 1 subunit cacophony form boutons. The synaptogenic function of α 2 δ-3 requires only the α 2 peptide, whose expression suffices to rescue bouton formation. Our results indicate that α 2 δ proteins have functions independent of their roles in the biophysics and localization of Ca 2+ channels, and synaptic architecture depends on these novel functions.
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