Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400005, India.
Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany.
Chemistry. 2021 May 12;27(27):7533-7541. doi: 10.1002/chem.202100328. Epub 2021 Mar 12.
Serotonin, an important signaling molecule in humans, has an unexpectedly high lipid membrane affinity. The significance of this finding has evoked considerable speculation. Here we show that membrane binding by serotonin can directly modulate membrane properties and cellular function, providing an activity pathway completely independent of serotonin receptors. Atomic force microscopy shows that serotonin makes artificial lipid bilayers softer, and induces nucleation of liquid disordered domains inside the raft-like liquid-ordered domains. Solid-state NMR spectroscopy corroborates this data at the atomic level, revealing a homogeneous decrease in the order parameter of the lipid chains in the presence of serotonin. In the RN46A immortalized serotonergic neuronal cell line, extracellular serotonin enhances transferrin receptor endocytosis, even in the presence of broad-spectrum serotonin receptor and transporter inhibitors. Similarly, it increases the membrane binding and internalization of oligomeric peptides. Our results uncover a mode of serotonin-membrane interaction that can potentiate key cellular processes in a receptor-independent fashion.
血清素是人类中一种重要的信号分子，它对脂膜具有出人意料的高亲和力。这一发现的意义引发了大量的推测。在这里，我们表明，血清素与膜的结合可以直接调节膜性质和细胞功能，提供一条完全独立于血清素受体的活性途径。原子力显微镜显示，血清素使人工脂双层变软，并在类脂筏样的无序域内诱导液体无序域的成核。固态 NMR 光谱在原子水平上证实了这一数据，表明在存在血清素的情况下，脂质链的有序参数呈均匀下降。在 RN46A 永生化血清素能神经元细胞系中，细胞外血清素增强转铁蛋白受体的内吞作用，即使存在广谱血清素受体和转运体抑制剂也是如此。同样，它增加了寡肽的膜结合和内化。我们的结果揭示了一种血清素-膜相互作用的模式，它可以以非受体依赖的方式增强关键的细胞过程。
