Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Neurosci. 2010 Jan 6;30(1):131-47. doi: 10.1523/JNEUROSCI.3282-09.2010.
Many bioactive neuropeptides containing RFamide at their C terminus have been described in both invertebrates and vertebrates. To obtain insight into the functional logic of RFamide signaling, we investigate it here in the feeding system of Aplysia. We focus on the expression, localization, and actions of two families of RFamide peptides, the FRFamides and FMRFamide, in the central neuronal circuitry and the peripheral musculature that generate the feeding movements. We describe the cloning of the FRFamide precursor protein and show that the FRFamides and FMRFamide are derived from different precursors. We map the expression of the FRFamide and FMRFamide precursors in the feeding circuitry using in situ hybridization and immunostaining and confirm proteolytic processing of the FRFamide precursor by mass spectrometry. We show that the two precursors are expressed in different populations of sensory neurons in the feeding system. In a representative feeding muscle, we demonstrate the presence of both FRFamides and FMRFamide and their release, probably from the processes of the sensory neurons in the muscle. Both centrally and in the periphery, the FRFamides and FMRFamide act in distinct ways, apparently through distinct mechanisms, and nevertheless, from an overall functional perspective, their actions are complementary. Together, the FRFamides and FMRFamide convert feeding motor programs from ingestive to egestive and depress feeding muscle contractions. We conclude that these structurally related peptides, although derived from different precursors, expressed in different neurons, and acting through different mechanisms, remain related to each other in the functional roles that they play in the system.
许多含有 RFamide 末端的生物活性神经肽已在无脊椎动物和脊椎动物中被描述。为了深入了解 RFamide 信号的功能逻辑，我们在此研究了其在 Aplysia 的摄食系统中的作用。我们重点研究了两种 RFamide 肽家族，即 FRFamides 和 FMRFamide，在产生摄食运动的中枢神经元回路和外周肌肉中的表达、定位和作用。我们描述了 FRFamide 前体蛋白的克隆，并表明 FRFamides 和 FMRFamide 源自不同的前体。我们通过原位杂交和免疫染色来绘制 FRFamide 和 FMRFamide 前体在摄食回路中的表达图谱，并通过质谱证实 FRFamide 前体的蛋白水解加工。我们表明，这两种前体在摄食系统中的不同感觉神经元群体中表达。在一个代表性的摄食肌肉中，我们证明了 FRFamides 和 FMRFamide 的存在及其释放，可能来自肌肉中感觉神经元的过程。无论是在中枢还是外周，FRFamides 和 FMRFamide 都以不同的方式发挥作用，显然通过不同的机制，但从整体功能角度来看，它们的作用是互补的。总之，FRFamides 和 FMRFamide 将摄食运动程序从摄取转变为排出，并抑制摄食肌肉收缩。我们得出结论，这些结构相关的肽，尽管源自不同的前体，在不同的神经元中表达，通过不同的机制发挥作用，但它们在系统中发挥的功能作用仍然相互关联。
