McCabe Brian D, Marqués Guillermo, Haghighi A Pejmun, Fetter Richard D, Crotty M Lisa, Haerry Theodore E, Goodman Corey S, O'Connor Michael B
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Neuron. 2003 Jul 17;39(2):241-54. doi: 10.1016/s0896-6273(03)00426-4.
We show that the BMP ortholog Gbb can signal by a retrograde mechanism to regulate synapse growth of the Drosophila neuromuscular junction (NMJ). gbb mutants have a reduced NMJ synapse size, decreased neurotransmitter release, and aberrant presynaptic ultrastructure. These defects are similar to those we observe in mutants of BMP receptors and Smad transcription factors. However, whereas these BMP receptors and signaling components are required in the presynaptic motoneuron, Gbb expression is required in large part in postsynaptic muscles; gbb expression in muscle rescues key aspects of the gbb mutant phenotype. Consistent with this notion, we find that blocking retrograde axonal transport by overexpression of dominant-negative p150/Glued in neurons inhibits BMP signaling in motoneurons. These experiments reveal that a muscle-derived BMP retrograde signal participates in coordinating neuromuscular synapse development and growth.
我们发现，骨形态发生蛋白（BMP）的直系同源物Gbb可通过逆行机制发出信号，以调节果蝇神经肌肉接头（NMJ）的突触生长。gbb突变体的NMJ突触尺寸减小，神经递质释放减少，突触前超微结构异常。这些缺陷与我们在BMP受体和Smad转录因子突变体中观察到的缺陷相似。然而，虽然这些BMP受体和信号传导成分在突触前运动神经元中是必需的，但Gbb表达在很大程度上在突触后肌肉中是必需的；肌肉中的gbb表达挽救了gbb突变体表型的关键方面。与此观点一致，我们发现通过在神经元中过表达显性负性p150/Glued来阻断逆行轴突运输会抑制运动神经元中的BMP信号传导。这些实验表明，肌肉衍生的BMP逆行信号参与协调神经肌肉突触的发育和生长。
