Coyle Ian P, Koh Young-Ho, Lee Wyan-Ching Mimi, Slind Jessica, Fergestad Tim, Littleton J Troy, Ganetzky Barry
Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA.
Neuron. 2004 Feb 19;41(4):521-34. doi: 10.1016/s0896-6273(04)00016-9.
We describe the isolation and characterization of nwk (nervous wreck), a temperature-sensitive paralytic mutant that causes excessive growth of larval neuromuscular junctions (NMJs), resulting in increased synaptic bouton number and branch formation. Ultrastructurally, mutant boutons have reduced size and fewer active zones, associated with a reduction in synaptic transmission. nwk encodes an FCH and SH3 domain-containing adaptor protein that localizes to the periactive zone of presynaptic terminals and binds to the Drosophila ortholog of Wasp (Wsp), a key regulator of actin polymerization. wsp null mutants display synaptic overgrowth similar to nwk and enhance the nwk morphological phenotype in a dose-dependent manner. Evolutionarily, Nwk belongs to a previously undescribed family of adaptor proteins that includes the human srGAPs, which regulate Rho activity downstream of Robo receptors. We propose that Nwk controls synapse morphology by regulating actin dynamics downstream of growth signals in presynaptic terminals.
我们描述了nwk（神经紊乱）的分离和特征，它是一种温度敏感的麻痹突变体，会导致幼虫神经肌肉接头（NMJ）过度生长，从而增加突触小体数量和分支形成。在超微结构上，突变体小体尺寸减小且活性区减少，这与突触传递减少有关。nwk编码一种含有FCH和SH3结构域的衔接蛋白，该蛋白定位于突触前终末的活性区周围，并与肌动蛋白聚合的关键调节因子Wasp（Wsp）的果蝇直系同源物结合。wsp缺失突变体表现出与nwk相似的突触过度生长，并以剂量依赖的方式增强nwk的形态学表型。在进化上，Nwk属于一个以前未描述的衔接蛋白家族，其中包括人类srGAPs，它们在Robo受体下游调节Rho活性。我们提出，Nwk通过调节突触前终末生长信号下游的肌动蛋白动力学来控制突触形态。
