Department of Cellular and Integrative Physiology, Long School of Medicine, University of Texas Health, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
University of Colorado School of Medicine, 12631 E. 17th Avenue B177, Aurora, CO, 80045, USA.
Sci Rep. 2018 Nov 26;8(1):17337. doi: 10.1038/s41598-018-35618-7.
Neurexins are well known trans-synaptic cell adhesion molecules that are required for proper synaptic development and function across species. Beyond synapse organization and function, little is known about other roles Neurexins might have in the nervous system. Here we report novel phenotypic consequences of mutations in Drosophila neurexin (dnrx), which alters axonal microtubule organization and transport. We show that dnrx mutants display phenotypic similarities with the BMP receptor wishful thinking (wit) and one of the downstream effectors, futsch, which is a known regulator of microtubule organization and stability. dnrx has genetic interactions with wit and futsch. Loss of Dnrx also results in reduced levels of other downstream effectors of BMP signaling, phosphorylated-Mad and Trio. Interestingly, postsynaptic overexpression of the BMP ligand, Glass bottom boat, in dnrx mutants partially rescues the axonal transport defects but not the synapse undergrowth at the neuromuscular junctions. These data suggest that Dnrx and BMP signaling are involved in many diverse functions and that regulation of axonal MT organization and transport might be distinct from regulation of synaptic growth in dnrx mutants. Together, our work uncovers a novel function of Drosophila Neurexin and may provide insights into functions of Neurexins in vertebrates.
神经连接蛋白是众所周知的跨突触细胞黏附分子，对于物种间突触的正常发育和功能至关重要。除了突触的组织和功能外，人们对神经连接蛋白在神经系统中的其他作用知之甚少。在这里，我们报告了果蝇神经连接蛋白（dnrx）突变的新表型后果，这些突变改变了轴突微管的组织和运输。我们发现 dnrx 突变体表现出与 BMP 受体如意（wit）及其下游效应物 futsch 相似的表型，后者是微管组织和稳定性的已知调节剂。dnrx 与 wit 和 futsch 存在遗传相互作用。Dnrx 的缺失也导致 BMP 信号转导的其他下游效应物，磷酸化-Mad 和 Trio 的水平降低。有趣的是，在 dnrx 突变体中过表达 BMP 配体 Glass bottom boat 部分挽救了轴突运输缺陷，但不能挽救神经肌肉接头处突触的过度生长。这些数据表明，Dnrx 和 BMP 信号转导参与了许多不同的功能，并且轴突 MT 组织和运输的调节可能与 dnrx 突变体中突触生长的调节不同。总之，我们的工作揭示了果蝇神经连接蛋白的新功能，并可能为神经连接蛋白在脊椎动物中的功能提供新的见解。
