将载荷定位到巨核细胞内的非传统分泌系统允许从血小板释放转基因蛋白质
Nathan L Asquith1, Isabelle C Becker2, Mark T Scimone3
1Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/NathanAsquith1.
Journal of thrombosis and haemostasis : JTH
|August 9, 2024
概括
血小板利用密集的管状系统 (DTS) 来进行货物运输. 添加KDEL序列可以将治疗性蛋白质包装成用于细胞治疗的血小板.
科学领域:
- 细胞生物学 细胞生物学
- 血液学 血液学 血液学
- 生物技术是生物技术.
背景情况:
- 血小板对于血液静止,血栓形成,癌症转移和感染至关重要.
- 血小板激活涉及细胞骨变化和脱粒化.
- 密集管状系统 (DTS) 是血管类硫醇异构酶的血小板分泌系统,但其货物运输不清楚.
研究的目的:
- 研究DTS货物运输在血小板中的机制.
- 通过DTS探索治疗性蛋白质包装成血小板.
主要方法:
- 使用逆转录病毒表达系统和共聚焦显微镜来追踪DTS货物 (eGFP-PDI).
- 采用小鼠骨髓移植模型来评估血小板释放的治疗性蛋白质.
主要成果:
- 蛋白质二硫化物异构酶上的KDEL检索动机对于DTS颗粒运输至关重要.
- 删除KDEL导致了异常包装和克拉林涂层内分泌体的上调.
- 异位蛋白 (组织因子通路抑制剂,介质素2) 用KDEL序列被包装成巨核细胞和血小板.
结论:
- 血小板分泌系统 (DTS) 作为血小板中的非正规分泌系统.
- 在体外生成的巨核细胞和血小板可以在细胞治疗中作为转基因蛋白质的输送载体.
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