DNA X激活蛋白12(DNAX activation protein of 12 kDa,DAP12)是包含基于免疫受体酪氨酸激活基序(immune receptor tyrosine activated motif,ITAM)的I型跨膜衔接蛋白的成员。DAP12与髓样细胞触发受体2(trigger receptor expressed in my...DNA X激活蛋白12(DNAX activation protein of 12 kDa,DAP12)是包含基于免疫受体酪氨酸激活基序(immune receptor tyrosine activated motif,ITAM)的I型跨膜衔接蛋白的成员。DAP12与髓样细胞触发受体2(trigger receptor expressed in myeloid cell 2,TREM-2)表达的触发受体形成分子复合物。牙周炎是口腔常见的一种慢性感染性疾病,牙周炎发生发展中,骨破坏和骨形成的调控信号通路会发生异常变化,而TREM-2/DAP12复合物在破骨细胞的生成和分化中起着重要的作用。本文总结了近年来TREM-2/DAP12复合物在牙周炎中作用的研究进展,以期为牙周炎的治疗提供新思路。展开更多
神经病理性疼痛困扰着数以百万人,目前,临床上对这种顽固性疼痛的治疗是一个紧迫的问题。一直以来,人们认为神经病理性疼痛是由神经元异常所引起的,近来大量研究表明,小胶质细胞对神经病理性疼痛的发生发展也起着重要作用。神经损伤后,T...神经病理性疼痛困扰着数以百万人,目前,临床上对这种顽固性疼痛的治疗是一个紧迫的问题。一直以来,人们认为神经病理性疼痛是由神经元异常所引起的,近来大量研究表明,小胶质细胞对神经病理性疼痛的发生发展也起着重要作用。神经损伤后,TREM2(triggering receptor expressed on myeloid cells 2)和DAP12(DNAX-activating protein of molecular mass 12 kDa)表达于脊髓背角的小胶质细胞,通过激活小胶质细胞,促进促炎因子分泌,从而加深了疼痛反应。展开更多
CD200:CD200R interactions regulate immune responses. Since CD200Rs show extensive homology in their extracellular region, generating anti-CD200R specific antibodies is a challenge. We report below on the generation of...CD200:CD200R interactions regulate immune responses. Since CD200Rs show extensive homology in their extracellular region, generating anti-CD200R specific antibodies is a challenge. We report below on the generation of mAbs specific for murine (m)R1/R2 and evidence that mR2 is expressed on the cell surface in the absence of the adaptor protein Dap12. Despite homology between mR1 and mR4, the unexpected reduction in the molecular mass (i.e. 90kDa vs 48kDa) between the two receptors suggested that the TM and cytoplasmic region of mR4 regulated glycosylation. Substitution of the TM and cytoplasmic region of mR1 and mR2 with that of mR4 reduced glycosylation of the chimeric receptors mR1r4 and mR2r4 implying that these regions regulated the glycosylation of mCD200Rs. In activation experiments, phosphorylation of Dap12 following interaction with CD200 occurred on cells expressing mR2V5 but not mR4V5. Similar experiments with the chimeric receptors mR1r2 and mR1r4 also produced phosphorylation of Dap12. Our data suggest that the TM and cytoplasmic region of mCD200Rs dictate their state of glycosylation and provide further evidence that both mCD200R1 and mCD200R2 bind CD200 as ligand with functional consequences for down-stream signaling.展开更多
文摘神经病理性疼痛困扰着数以百万人,目前,临床上对这种顽固性疼痛的治疗是一个紧迫的问题。一直以来,人们认为神经病理性疼痛是由神经元异常所引起的,近来大量研究表明,小胶质细胞对神经病理性疼痛的发生发展也起着重要作用。神经损伤后,TREM2(triggering receptor expressed on myeloid cells 2)和DAP12(DNAX-activating protein of molecular mass 12 kDa)表达于脊髓背角的小胶质细胞,通过激活小胶质细胞,促进促炎因子分泌,从而加深了疼痛反应。
文摘CD200:CD200R interactions regulate immune responses. Since CD200Rs show extensive homology in their extracellular region, generating anti-CD200R specific antibodies is a challenge. We report below on the generation of mAbs specific for murine (m)R1/R2 and evidence that mR2 is expressed on the cell surface in the absence of the adaptor protein Dap12. Despite homology between mR1 and mR4, the unexpected reduction in the molecular mass (i.e. 90kDa vs 48kDa) between the two receptors suggested that the TM and cytoplasmic region of mR4 regulated glycosylation. Substitution of the TM and cytoplasmic region of mR1 and mR2 with that of mR4 reduced glycosylation of the chimeric receptors mR1r4 and mR2r4 implying that these regions regulated the glycosylation of mCD200Rs. In activation experiments, phosphorylation of Dap12 following interaction with CD200 occurred on cells expressing mR2V5 but not mR4V5. Similar experiments with the chimeric receptors mR1r2 and mR1r4 also produced phosphorylation of Dap12. Our data suggest that the TM and cytoplasmic region of mCD200Rs dictate their state of glycosylation and provide further evidence that both mCD200R1 and mCD200R2 bind CD200 as ligand with functional consequences for down-stream signaling.
