pH-dependent formation of membranous cytoplasmic body-like structure of ganglioside GM1/bis(monoacylglycero)phosphate mixed membranes
pH-dependent formation of membranous cytoplasmic body-like structure of ganglioside GM1/bis(monoacylglycero)phosphate mixed membranes
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DOI：
10.1529/biophysj.106.098657
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Kobayashi, Toshihide
中科院分区：
文献类型：
--
作者：
Hayakawa, Tomohiro;Makino, Asami;Kobayashi, Toshihide
通过冷冻断裂电子显微镜和小角X射线散射技术，在不同pH条件下对神经节苷脂G(M1)和内体特异性脂质双（单酰甘油）磷酸酯（BMP，也称为溶血双磷脂酸）混合物的膜结构进行了研究。在pH 8.5 - 6.5时，G(M1)/BMP（1:1摩尔/摩尔）混合物形成小的囊泡聚集体，而在酸性条件（pH 5.5，4.6）下该混合物形成紧密堆积的层状结构，层间距为8.06 nm。由于单独的BMP在较宽的pH值范围内呈现弥散的层状结构，而GM1形成胶束，结果表明G(M1)和BMP两者对于产生紧密堆叠的多层囊泡都是必需的。这些囊泡类似于患有G(M1)神经节苷脂沉积症患者细胞中的膜性细胞质体。与G(M1)神经节苷脂沉积症类似，胆固醇以依赖于G(M1)和低pH的方式被困在BMP囊泡中。采用不同神经节苷脂和一种G(M1)类似物的研究表明，G(M1)的糖链和唾液酸在G(M1)/BMP膜的pH依赖性结构变化中具有重要作用。
Membrane structures of the mixtures of ganglioside G(M1) and endosome specific lipid, bis (monoacylglycero) phosphate (BMP, also known as lysobisphosphatidic acid) were examined at various pH conditions by freeze-fracture electron microscopy and small- angle x- ray scattering. At pH 8.5 - 6.5, a G(M1)/BMP (1: 1 mol/mol) mixture formed small vesicular aggregates, whereas the mixture formed closely packed lamellar structures under acidic conditions (pH 5.5, 4.6) with the lamellar repeat distance of 8.06 nm. Since BMP alone exhibits a diffuse lamellar structure at a broad range of pH values and GM1 forms a micelle, the results indicate that both G(M1) and BMP are required to produce closely stacked multilamellar vesicles. These vesicles resemble membranous cytoplasmic bodies in cells derived from patients suffering from G(M1) gangliosidosis. Similar to G(M1) gangliosidosis, cholesterol was trapped in BMP vesicles in G(M1)- and in a low pH- dependent manner. Studies employing different gangliosides and a G(M1) analog suggest the importance of sugar chains and a sialic acid of G(M1) in the pH- dependent structural change of G(M1)/BMP membranes.