Store-operated cation entry mediated by CD20 in membrane rafts.
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.
Li
Haidong
H
Immunology Research Group, Department of Biochemistry and Molecular Biology, University of Calgary Health Sciences Center, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Ayer
Linda M
LM
Lytton
Jonathan
J
Deans
Julie P
JP
D000818:Animals; D018951:Antigens, CD20 / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000494:pharmacology; D006224:Cricetinae; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D017136:Ion Transport; D021962:Membrane Microdomains / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013324:Strontium / Q000378:metabolism
D018951:Antigens, CD20; D015220:Calcium Channels; D034741:RNA, Small Interfering; D002784:Cholesterol; D002118:Calcium; D013324:Strontium