TY - JOUR TI - Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104 AU - Li, Jiaxing AU - Zhang, Yao V AU - Asghari Adib, Elham AU - Stanchev, Doychin T AU - Xiong, Xin AU - Klinedinst, Susan AU - Soppina, Pushpanjali AU - Jahn, Thomas Robert AU - Hume, Richard I AU - Rasse, Tobias M AU - Collins, Catherine A A2 - VijayRaghavan, K VL - 6 PY - 2017 DA - 2017/09/19 SP - e24271 C1 - eLife 2017;6:e24271 DO - 10.7554/eLife.24271 UR - https://doi.org/10.7554/eLife.24271 AB - The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon. KW - axonal transport KW - kinesin KW - synapse KW - signaling KW - stress response JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -