LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell.
LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell.
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DOI：
10.1093/intimm/dxl031
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发表时间：
2006-06
影响因子：
4.4
通讯作者：
J. Shirakawa;Yinan Wang;S. Tahara-Hanaoka;S. Honda;K. Shibuya;A. Shibuya
中科院分区：
文献类型：
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作者：
J. Shirakawa;Yinan Wang;S. Tahara-Hanaoka;S. Honda;K. Shibuya;A. Shibuya
在TCR识别抗原后，白细胞粘附分子DNAM-1和白细胞功能相关抗原-1（LFA-1）与脂筏结合并形成外周超分子活化簇，其围绕免疫突触处的中央超分子活化簇。DNAM-1的胞质尾中的丝氨酸残基负责DNAM-1与脂筏的这种缔合。TCR介导的信号还诱导DNAM-1与LFA-1的物理缔合，DNAM-1的丝氨酸磷酸化也是其原因。然而，丝氨酸残基如何参与DNAM-1的脂筏募集仍不清楚。在这里，我们表明，虽然TCR介导的信号诱导DNAM-1的丝氨酸磷酸化，但DNAM-1不与来自LFA-1表达缺陷小鼠的CD 4 + T细胞中的脂筏相关，表明DNAM-1的脂筏募集依赖于LFA-1的表达。这些结果表明，DNAM-1的丝氨酸磷酸化主要诱导DNAM-1与LFA-1的物理结合，然后将DNAM-1带入脂筏区室。
Upon antigen recognition by the TCR, both the leukocyte adhesion molecules DNAM-1 and leukocyte function-associated antigen-1 (LFA-1) associate with lipid rafts and form peripheral supra-molecular activation clusters that surround central-supra-molecular activation clusters at the immunological synapse. The serine residue in the cytoplasmic tail of DNAM-1 is responsible for this association of DNAM-1 with lipid rafts. The TCR-mediated signal also induces physical association of DNAM-1 with LFA-1, for which the serine phosphorylation of DNAM-1 is also responsible. However, how the serine residue is involved in lipid raft recruitment of DNAM-1 has remained unclear. Here, we show that, although the TCR-mediated signal induced the serine phosphorylation of DNAM-1, DNAM-1 did not associate with lipid rafts in CD4+ T cells derived from mice deficient in LFA-1 expression, indicating that lipid raft recruitment of DNAM-1 depends on LFA-1 expression. These results suggest that the serine phosphorylation of DNAM-1 primarily induces physical association of DNAM-1 with LFA-1, which then takes DNAM-1 into lipid raft compartment.