Baumann Nicole, Colsch Benoît, Lefèvre Mireille, Portoukalian Jacques
Laboratoire de neurochimie INSERM U 495, Hôpital de la Salpêtrière, 75651 Paris.
J Soc Biol. 2003;197(3):205-10.
During the past years, the notion of microdomains at the surface of cellular membranes has been developed. These are constituted by lipid rafts which involve sphingoglycolipids and cholesterol. To these rafts are associated proteins which have a lipid anchor or are transmembrane proteins. These lipid rafts target specific proteins at the plasma membrane surface and can remain associated with them. They are present in surface receptors and endocytosis occurs upon binding of the specific ligands. Thus these rafts participate to major aspects of cellular dynamics. These rafts are complex structures, insoluble in non-ionic detergents. According to the detergent used, many types of rafts can be isolated. Any alteration of cholesterol, sphingoglycolipids, or abnormalities of the proteins themselves, can lead to abnormal targeting at the membrane surface. It is possible that specific sphingoglycolipids are necessary to target specific proteins at the membrane surface. This may explain the complexity of the sphingoglycolipid molecules, both in relation to their oligosaccharide and to their ceramide structures. There is both a cellular and a tissue specificity of these constituents. Complex sphingoglycolipids are involved in cellular differentiation, cellular polarization, and modified in relation to cancer. Virus and bacteria can be linked to the sphingoglycolipids of these microdomains and alter cellular signaling and function. Sphingoglycolipids are involved in autoimmune diseases as antibody targets and in neurolipidoses which are genetic diseases involving their catabolism. The dynamics of the lipid rafts, in relation to cholesterol, can be altered in Niemann-Pick's disease type C and in Alzheimer's disease. Thus these microdomains are involved in many aspects related to normal and pathological cellular dynamics.
在过去几年里，细胞膜表面微区的概念得以发展。这些微区由富含鞘糖脂和胆固醇的脂筏构成。与这些脂筏相关联的是具有脂质锚定或为跨膜蛋白的蛋白质。这些脂筏在质膜表面靶向特定蛋白质并可与之保持关联。它们存在于表面受体中，特异性配体结合后会发生内吞作用。因此，这些脂筏参与细胞动态的主要方面。这些脂筏是复杂的结构，不溶于非离子去污剂。根据所使用的去污剂不同，可以分离出多种类型的脂筏。胆固醇、鞘糖脂的任何改变或蛋白质本身的异常，都可能导致膜表面靶向异常。特定的鞘糖脂可能是在膜表面靶向特定蛋白质所必需的。这或许可以解释鞘糖脂分子在其寡糖和神经酰胺结构方面的复杂性。这些成分存在细胞和组织特异性。复杂的鞘糖脂参与细胞分化、细胞极化，并在癌症中发生改变。病毒和细菌可与这些微区的鞘糖脂相连，改变细胞信号传导和功能。鞘糖脂作为自身免疫性疾病中的抗体靶点以及参与神经鞘脂贮积病（涉及它们分解代谢的遗传性疾病）。在尼曼 - 匹克病C型和阿尔茨海默病中，脂筏与胆固醇相关的动态变化可能会改变。因此，这些微区涉及与正常和病理细胞动态相关的许多方面。
