Connectivity changes in developing neuronal circuits involve large and small scale rearrangements of the underlying cytoskeleton. While changes to the microtubule (MT) cytoskeleton during dendritic plasticity have been well characterized, much less is known about how MT dynamics contributes to structural plasticity of pre-synaptic terminals. In C. elegans, the GABAergic DD neurons undergo synapse remodeling in the L1-L2 molt, termed DD remodeling, where pre-existing ventral synapses are eliminated and new synapses are formed along the dorsal neurite, without neurite growth or pruning (White et al., 1978). Here we characterize the role of the MT cytoskeleton in DD remodeling, using a double mutant animal containing a missense mutation in α-tubulin (tba-1(gf)) (Baran et al., 2010) and loss of the conserved MAPKKK DLK-1 (dlk-1(0)) (Nakata et al., 2005). DD remodeling is completely blocked in tba-1(gf) dlk-1(0) animals, and temporal activation of DLK-1 in the L2 stage restores DD remodeling. MT polarity is largely unchanged before and after DD remodeling, while a loss in dynamic MTs causes the failure in DD remodeling in tba-1(gf) dlk-1(0). We hypothesized that an increase in dynamic MTs is critical for axonal transport during new synapse formation. In support of this hypothesis, 4-D imaging during DD remodeling shows a significant reduction in SNB-1::GFP labeled vesicles trafficked from the ventral to the dorsal neurite in tba-1(gf) dlk-1(0) animals. Moreover, we identify gain-of-function alleles in Kinesin-1/UNC-116 that suppress tba-1(gf) dlk-1(0), through an increase in MT-motor binding affinity that promotes synaptic vesicle transport during DD remodeling. In summary, our data provides in vivo evidence of the importance of temporal regulation of dynamic MTs, under the control of DLK-1, in facilitating circuit plasticity.
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