Kinoshita Masanao, Matsumori Nobuaki
Department of Chemistry, Graduate School of Science, Kyushu University, Fukuoka 819-0395, Japan.
Membranes (Basel). 2022 Jul 23;12(8):727. doi: 10.3390/membranes12080727.
Ceramide is the simplest precursor of sphingolipids and is involved in a variety of biological functions ranging from apoptosis to the immune responses. Although ceramide is a minor constituent of plasma membranes, it drastically increases upon cellular stimulation. However, the mechanistic link between ceramide generation and signal transduction remains unknown. To address this issue, the effect of ceramide on phospholipid membranes has been examined in numerous studies. One of the most remarkable findings of these studies is that ceramide induces the coalescence of membrane domains termed lipid rafts. Thus, it has been hypothesised that ceramide exerts its biological activity through the structural alteration of lipid rafts. In the present article, we first discuss the characteristic hydrogen bond functionality of ceramides. Then, we showed the impact of ceramide on the structures of artificial and cell membranes, including the coalescence of the pre-existing lipid raft into a large patch called a signal platform. Moreover, we proposed a possible structure of the signal platform, in which sphingomyelin/cholesterol-rich and sphingomyelin/ceramide-rich domains coexist. This structure is considered to be beneficial because membrane proteins and their inhibitors are separately compartmentalised in those domains. Considering the fact that ceramide/cholesterol content regulates the miscibility of those two domains in model membranes, the association and dissociation of membrane proteins and their inhibitors might be controlled by the contents of ceramide and cholesterol in the signal platform.
神经酰胺是鞘脂最简单的前体，参与从细胞凋亡到免疫反应等多种生物学功能。尽管神经酰胺是质膜的次要成分，但在细胞受到刺激时会急剧增加。然而，神经酰胺生成与信号转导之间的机制联系仍然未知。为了解决这个问题，众多研究中都检测了神经酰胺对磷脂膜的影响。这些研究最显著的发现之一是神经酰胺会诱导称为脂筏的膜结构域发生聚集。因此，有人推测神经酰胺通过脂筏的结构改变发挥其生物学活性。在本文中，我们首先讨论神经酰胺特有的氢键功能。然后，我们展示了神经酰胺对人工膜和细胞膜结构的影响，包括将预先存在的脂筏聚集成一个称为信号平台的大斑块。此外，我们提出了信号平台的一种可能结构，其中富含鞘磷脂/胆固醇的结构域和富含鞘磷脂/神经酰胺的结构域共存。这种结构被认为是有益的，因为膜蛋白及其抑制剂在这些结构域中被分别分隔开来。考虑到神经酰胺/胆固醇含量调节模型膜中这两个结构域的互溶性这一事实，膜蛋白及其抑制剂的结合和解离可能受信号平台中神经酰胺和胆固醇含量的控制。
