4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

Abstract

BackgroundProtein 4.1R is an important component of the 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 counterpart. ConclusionsGlycophorin 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. CD44 and CD47 glycoproteins. Haematologica 2009;94:1354-1361. doi:10.3324/haematol.2009 This is an open-access paper. 4.1R-deficient human red blood cells have altered phosphatidylserine exposure pathways and are deficient in CD44 and CD47 glycoproteins

Alterations of Red Cell Membrane Properties in Nneuroacanthocytosis

“…Moreover, both spectrin and protein 4.1 have been shown to directly bind to the membrane by fatty acid posttranslational modification [34] and/or association with PS [35,36]. Spectrin is thought to be involved in the formation of large PS-rich lipid domains [35] and protein 4.1-deficient red blood cells show alterations in pathways associated with PS-exposure [37]. Thus it is conceivable that the cytoskeleton is also involved in the regulation of membrane phospholipid asymmetry.…”

Effect of substances with cryoprotective properties on surface marker CD44 in human erythrocytes

“…Change in the dynamics of the protein interactions in this complex may affect the expression of the surface marker CD44. By way of example in the erythrocytes from the patients with the genetically caused deficiency of the protein 4.1, the decrease in the CD44 expression was also detected [55]. If one assumes that the attenuation of the interactions in the system of protein macrocomplexes take place in the presence of the cryoprotectants, then the loss of CD44 would increase.…”

“…In human erythrocytes, CD44 is able to interact with the cytoskeleton through ankyrin and protein 4.1 [54]. Furthermore, CD44 with another surface marker CD47 are involved in the formation of the macrocomplexes with the involvement of the protein 4.1 [55]. Change in the dynamics of the protein interactions in this complex may affect the expression of the surface marker CD44.…”

Changes in Erythrocyte Surface Marker Cd44 During Hypothermic and Low Temperature Storage

“…Ці зв'язки є динамічними і можуть відрізнятися в різних ділянках мембрани [3,4]. В еритро-цитах людини виявлена здатність CD44 взає-модіяти з цитоскелетом через анкірин і білок смуги 4.1 [20,21]. Раніше було показано, що зміна білкових взаємодій у макромолеку-лярному комплексі до складу, якого входять білок смуги 4.1 та CD44 може впливати на експресію поверхневого маркера CD44, спри-яючи її зниженню [21].…”

“…В еритро-цитах людини виявлена здатність CD44 взає-модіяти з цитоскелетом через анкірин і білок смуги 4.1 [20,21]. Раніше було показано, що зміна білкових взаємодій у макромолеку-лярному комплексі до складу, якого входять білок смуги 4.1 та CD44 може впливати на експресію поверхневого маркера CD44, спри-яючи її зниженню [21]. Якщо припустити, що під впливом факторів середовища в процесі кріоконсервування ослаблюються взаємодії в системі цього макрокомплекса білків, то втрата CD44 буде посилюватися.…”