Kinetic propertie of three Darier disease SERCA26 mutants.

探讨了Darier病致病钙ATPase(Serca2B)突变体的功能异常。在51个突变株中，15个突变株的SERCA2b表达可忽略不计，21个突变株的ATPase活性为阴性，8个突变株的ATPase和钙泵活性在功能上解偶联。其余3例表现出独特的特征。它们表现出几乎正常的表达，高ATPase和偶联钙转运活性，与野生型基本相同(L321F)或略低(I274V和M719I)。M719I和L321F对胞浆钙的亲和力降低2-3倍，而I274V具有正常的高亲和力。L321F对鲁米诺钙蓄积对转运周期的反馈抑制的敏感性也显著降低。因此，引起ATPase(SERCA2b)的Darier病的不同异常在Cos1细胞中显示出不同类型的钙稳态改变。

The functional abnormalities in Darier disease-causing calcium ATPase (Serca2B) mutants were explored. Among 51mutants, 15 showed negligible expression of SERCA2b, 21 showed negative ATPase activities, and 8 showed functional uncoupling of ATPase and calcium pump activities in Cos1 cells. The remaining 3 showed unique characteristics. They exhibited nearly normal expression, high ATPase and coupled calcium transport activities that were essentially identical (L321F) or slightly lower (I274V and M719I) as compared with those of the wild type. M719I and L321F possess 2-3 fold reduced affinity for cytoplasmic calcium, whereas I274V possesses the normal high affinity. L321F exhibited also the remarkably reduced sensitivity to the feedback inhibition of the transport cycle by accumulated luminal calcium. Thus different abnormalities in Darier disease causing ATPase (SERCA2b) showed distinct types of altered calcium homeostasis in Cos1 cells.