Li Haidong, Ayer Linda M, Lytton Jonathan, Deans Julie P
Immunology Research Group, Department of Biochemistry and Molecular Biology, University of Calgary Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
J Biol Chem. 2003 Oct 24;278(43):42427-34. doi: 10.1074/jbc.M308802200. Epub 2003 Aug 14.
B cell activation requires sustained elevation of cytoplasmic free calcium, achieved by influx through store-operated calcium (SOC) channels. The molecular identity of these channels is not known. Ectopic expression of the raft-associated tetraspan protein CD20 in Chinese hamster ovary cells introduced a novel SOC entry pathway that was permeable to strontium as well as to calcium. The activity of this SOC pathway was abolished by deletion of a cytoplasmic sequence in CD20 essential for its efficient raft localization. Strontium-permeable SOC channels were detected in B cells, and B cell receptor-stimulated influx was significantly reduced by downregulation of CD20 expression using short interfering RNA and also by cholesterol depletion. This is the first evidence that raft-associated CD20 constitutes a component of a SOC entry pathway activated by the B cell receptor.
B细胞活化需要细胞质游离钙持续升高，这是通过经储存-操纵性钙（SOC）通道内流来实现的。这些通道的分子身份尚不清楚。在中国仓鼠卵巢细胞中异位表达与脂筏相关的四跨膜蛋白CD20引入了一种新型的SOC进入途径，该途径对锶和钙均具有通透性。通过缺失CD20中对其有效定位于脂筏至关重要的细胞质序列，可消除该SOC途径的活性。在B细胞中检测到了对锶通透的SOC通道，使用短干扰RNA下调CD20表达以及通过胆固醇耗竭均可显著减少B细胞受体刺激的内流。这是首个证据表明与脂筏相关的CD20构成了由B细胞受体激活的SOC进入途径中的一个组分。
