Full activation without calmodulin of calmodulin‐dependent cyclic nucleotide phosphodiesterase by acidic glycosphingolipids: GM3, sialosylneolactotetraosylceramide and sulfatide

[摘要]

Among calmodulin-non-binding glycosphingolipids, GM3, sialosylneolactotetraosylceramide (LM1), and sulfatide potently activated calmodulin-dependent cyclic nucleotide phosphodiesterase with or without Ca²⁺ showing ED₅₀ 1–5 μM. In contrast to calmodulin-binding gangliosides, these glycosphingolipids activated the enzyme up to the maximum level achieved by Ca²⁺/calmodulin and did not inhibit the activity at higher concentrations. Competition studies with GD1b that bind both to calmodulin and the enzyme suggest that the calmodulin-non-binding glycosphingolipids activate the enzyme through interaction with the same site of the enzyme as GD1b interacts.

[学科分类] 生物化学/生物物理

[关键词] GM3;LM1;Sulfatide;Ganglioside;Calmodulin;cAMP-phosphodiesterase;CaM;calmodulin;dansyl;5-dimethylaminonaphthalene-1-sulfonyl;PDE;cyclic nucleotide phosphodiesterase. Abbreviations by Svennerholm [1] for gangliosides and IUPAC-IUB Recommendations for lipids [2] were used;GD1b;II3(NeuAca2-8NeuAc)-Gg4Cer;LM1;sialosylneolactotetraosylceramide;IV3Sialyl-nLc4Cer. Structures of the other glycosphingolipids are shown in Table I