4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins
4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins
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DOI：
10.3324/haematol.2009.006585
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发表时间：
2009-10-01
期刊：
影响因子：
--
通讯作者：
Avent, Neil D.
中科院分区：
文献类型：
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作者：
Jeremy, Kris P.;Plummer, Zoe E.;Avent, Neil D.
背景蛋白4.1R是红细胞膜骨架的重要组成部分。设计与方法以CD47糖蛋白和血糖蛋白C为配体，研究了CD47糖蛋白和糖蛋白C对两例4.1R缺乏症患者红细胞磷脂酰丝氨酸暴露的影响。结果CD47糖蛋白与CD47糖蛋白配体结合后，4.1R缺陷红细胞的磷脂酰丝氨酸暴露明显增加。自发的磷脂酰丝氨酸暴露是正常的。4.1R、血糖素C和P55缺失或急剧减少。CD47糖蛋白改变或缺失，CD44糖蛋白缺失。最近对4.1R缺陷小鼠的研究发现，人红细胞4.1R与其对应的小鼠红细胞之间的相互作用存在明显的功能差异。结论血糖素C已知与4.1R结合，我们先前已确定它也与CD47结合，我们认为4.1R在磷脂酰丝氨酸暴露信号通路中发挥作用，而磷脂酰丝氨酸暴露信号通路在红细胞周转中起重要作用，CD44与4.1R的连锁可能与这一过程有关
BackgroundProtein 4.1R is an important component of die red cell membrane skeleton. It imparts structural integrity and has transmembrane signaling roles by direct interactions with transmembrane proteins and other membrane skeletal components, notably p55 and calmodulin.Design and MethodsSpontaneous and ligation-induced phosphatidylserine exposure on erythrocytes from two patients with 4.1R deficiency were studied, using CD47 glycoprotein and glycophorin C as ligands We also looked for protein abnormalities in the 4.1R - based multiprotein complex.ResultsPhosphatidylserine exposure was significantly increased in 4.1R-deficient erythrocytes obtained from the two different individuals when ligands to CD47 glycoprotein were bound. Spontaneous phosphatidylserine exposure was normal. 4.1R, glycophorin C and p55 were missing or sharply reduced. Furthermore there was an alteration or deficiency of CD47 glycoprotein and a lack of CD44 glycoprotein. Based on a recent study in 4.1R-deficient mice, we found that there are clear functional differences between interactions of human red cell 4.1R and its murine counterpartConclusionsGlycophorin C is known to bind 4.1R, and we have defined previously that it also binds CD47 From our evidence, we suggest that 4.1R plays a role in the phosphatidylserine exposure signaling pathway that is of Fundamental importance in red cell turnover The linkage of CD44 to 4.1R may be relevant to this process