Kim Myung-Jun, O'Connor Michael B
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS One. 2014 Sep 25;9(9):e107443. doi: 10.1371/journal.pone.0107443. eCollection 2014.
Members of the TGF-β superfamily play numerous roles in nervous system development and function. In Drosophila, retrograde BMP signaling at the neuromuscular junction (NMJ) is required presynaptically for proper synapse growth and neurotransmitter release. In this study, we analyzed whether the Activin branch of the TGF-β superfamily also contributes to NMJ development and function. We find that elimination of the Activin/TGF-β type I receptor babo, or its downstream signal transducer smox, does not affect presynaptic NMJ growth or evoked excitatory junctional potentials (EJPs), but instead results in a number of postsynaptic defects including depolarized membrane potential, small size and frequency of miniature excitatory junction potentials (mEJPs), and decreased synaptic densities of the glutamate receptors GluRIIA and B. The majority of the defective smox synaptic phenotypes were rescued by muscle-specific expression of a smox transgene. Furthermore, a mutation in actβ, an Activin-like ligand that is strongly expressed in motor neurons, phenocopies babo and smox loss-of-function alleles. Our results demonstrate that anterograde Activin/TGF-β signaling at the Drosophila NMJ is crucial for achieving normal abundance and localization of several important postsynaptic signaling molecules and for regulating postsynaptic membrane physiology. Together with the well-established presynaptic role of the retrograde BMP signaling, our findings indicate that the two branches of the TGF-β superfamily are differentially deployed on each side of the Drosophila NMJ synapse to regulate distinct aspects of its development and function.
转化生长因子-β（TGF-β）超家族的成员在神经系统发育和功能中发挥着多种作用。在果蝇中，神经肌肉接头（NMJ）处的逆行骨形态发生蛋白（BMP）信号在突触前对于正常的突触生长和神经递质释放是必需的。在本研究中，我们分析了TGF-β超家族的激活素分支是否也对NMJ的发育和功能有贡献。我们发现，消除激活素/TGF-β I型受体babo或其下游信号转导分子smox，并不影响突触前NMJ的生长或诱发的兴奋性接头电位（EJP），但会导致一些突触后缺陷，包括膜电位去极化、微小兴奋性接头电位（mEJP）的幅度和频率变小，以及谷氨酸受体GluRIIA和B的突触密度降低。大多数有缺陷的smox突触表型通过肌肉特异性表达smox转基因得以挽救。此外，actβ（一种在运动神经元中强烈表达的激活素样配体）的突变模拟了babo和smox功能丧失等位基因的表型。我们的结果表明，果蝇NMJ处的顺行激活素/TGF-β信号对于实现几种重要突触后信号分子的正常丰度和定位以及调节突触后膜生理学至关重要。与逆行BMP信号在突触前已确立的作用一起，我们的发现表明TGF-β超家族的两个分支在果蝇NMJ突触的两侧以不同方式发挥作用，以调节其发育和功能的不同方面。
