The Shape Shifting Story of Reticulocyte Maturation

Ovchynnikova, Elina; Aglialoro, Francesca; Lindern, Marieke von; Akker, Emile van den

doi:10.3389/fphys.2018.00829

Cited by 54 publications

(53 citation statements)

References 159 publications

(218 reference statements)

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“…The concentrations of platelet-derived microvesicles, however, increased significantly after each marching day (Figure 4). The fraction of the most mature reticulocytes, as detected by the fraction of CD71-positive RBCs [20], decreased after the first day of marching, but increased again during the consecutive night (Figure 3). The fraction of the most mature reticulocytes, as detected by the fraction of CD71-positive RBCs [20], decreased after the first day of marching, but increased again during the consecutive night (Figure 3).…”

Section: Resultsmentioning

confidence: 97%

“…Mechanical stimulation plays a role in the final differentiation of cultured RBCs in vitro [20]. Thus, an exercise-associated increase in blood flow may stimulate exosome-mediated removal of RNA and fragments of cellular organelles, and may thereby accelerate the maturation of reticulocytes in vivo (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

“…APC-labeled anti-C3d (1 µg/million cells, Assay Pro, St. Louis, Missouri, USA) was used to evaluate the degree of complement-induced opsonization [19]. APC-labeled CD71 (clone CY1G4, 1:200, Biolegend, San Diego, California, USA) was used to measure the percentage of reticulocytes [20]. Staining of band 3 with eosin-5' maleimide (EMA, Thermo Fisher Scientific, Landsmeer, the Netherlands) was performed by incubating one million RBCs with 25 µL of EMA (0.5 mg/mL in Ringer's solution) in the dark at RT for 15 min [21,22].…”

Section: Flow Cytometrymentioning

confidence: 99%

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Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

et al. 2019

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Our knowledge on the molecular mechanisms of red blood cell aging is mostly derived from in vitro studies. The Four Days Marches of Nijmegen in the Netherlands, the world’s largest yearly walking event, constitutes a unique possibility to study the effect of mechanical and biochemical stressors occurring during moderate-intensity exercise on red blood cell aging in vivo. Therefore, longitudinal measurements were performed of biophysical, immunological, and functional red blood cell characteristics that are known to change during aging. Our data show that moderate-intensity exercise induces the generation of a functionally improved red blood cell population with a higher deformability and a decreased tendency to aggregate. This is likely to be associated with an early removal of the oldest red blood cells from the circulation, as deduced from the (dis)appearance of removal signals. Thus, the physiological red blood cell aging process maintains homeostasis in times of moderate-intensity exercise-induced stress, probably by accelerated aging and subsequent removal of the oldest, most vulnerable red blood cells.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

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Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

et al. 2019

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“…In a similar vein to the sperm maturation defects we report here, Fbxo7 has also been shown to be required during the final maturation steps of erythrocytes, and we have previously reported the Fbxo7 LacZ/LacZ mice are anaemic due to delayed mitophagy and defects in exiting cell cycle . Importantly, during this maturation step, macrophages in erythroblast islands phagocytose the shed organelles from maturing reticulocytes (Ovchynnikova et al, 2018;Zhang et al, 2015;Geminard et al, 2002), a process requiring the coupling of the autophagy and exocytosis pathways (Mankelow et al, 2015). Could this coupling be coordinated by Fbxo7?…”

Section: How Are the Germ Cells Eliminated In Fbxo7 Lacz/lacz Testes?mentioning

confidence: 99%

A conserved requirement forFbxo7during male germ cell cytoplasmic remodelling

Rathje

Randle

Skinner

et al. 2019

Preprint

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statementFbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here we show that in addition to the previously-known Parkinsonian and haematopoietic phenotypes, Fbxo7deficient male mice are completely sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the cells undergo cytoplasmic remodelling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7-deficient males. Mutation of the Drosophila Fbxo7 orthologue, nutcracker (ntc) was previously shown to cause sterility at a similar stage of germ cell development, indicating that the requirement for Fbxo7 is conserved.The ntc phenotype was attributed to proteasome mis-regulation via an interaction with the proteasome regulator, DmPI31. Our data suggest rather that in mice, the requirement for Fbxo7 is either independent of its interaction with PI31, or relates specifically to cytoplasmic proteasome activity during spermiogenesis.

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“…Reticulocytes (Retics) are the result of the enucleation in the bone marrow of their immediate nucleated precursor, the orthochromatic erythroblast, and still retain several components in their membrane and cytoplasm with an excess of approximately 20% of plasma membrane that must be removed. Part of the maturation occurs in the bone marrow, where the cells are defined as R1 Retics, part in the circulation (R2 Retics) where they will lose additional components and residual excess membrane before they attain the final structure of a fully functional and stable biconcave discocytic red blood cell (RBC) (Chasis et al, 1989;Moras et al, 2017;Ovchynnikova et al, 2018). In turn, RBCs lose membrane surface area and cell volume as they age in the circulation.…”

Section: Introductionmentioning

confidence: 99%

Membrane Rearrangements in the Maturation of Circulating Human Reticulocytes

et al. 2020

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Red blood cells (RBCs) begin their circulatory life as reticulocytes (Retics) after their egress from the bone marrow where, as R1 Retics, they undergo significant rearrangements in their membrane and intracellular components, via autophagic, proteolytic, and vesicle-based mechanisms. Circulating, R2 Retics must complete this maturational process, which involves additional loss of significant amounts of membrane and selected membrane proteins. Little is known about the mechanism(s) at the basis of this terminal differentiation in the circulation, which culminates with the production of a stable biconcave discocyte. The membrane of R1 Retics undergoes a selective remodeling through the release of exosomes that are enriched in transferrin receptor and membrane raft proteins and lipids, but are devoid of Band 3, glycophorin A, and membrane skeletal proteins. We wondered whether a similar selective remodeling occurred also in the maturation of R2 Retics. Peripheral blood R2 Retics, isolated by an immunomagnetic method, were compared with mature circulating RBCs from the same donor and their membrane protein and lipid content was analyzed. Results show that both Band 3 and spectrin decrease from R2 Retics to RBCs on a "per cell" basis. Looking at membrane proteins that are considered as markers of membrane rafts, flotillin-2 appears to decrease in a disproportionate manner with respect to Band 3. Stomatin also decreases but in a more proportionate manner with respect to Band 3, hinting at a heterogeneous nature of membrane rafts. High resolution lipidomics analysis, on the contrary, revealed that those lipids that are typically representative of the membrane raft phase, sphingomyelin and cholesterol, are enriched in mature RBCs with respct to Retics, relative to total cell lipids, strongly arguing in favor of the selective retention of at least certain subclasses of membrane rafts in RBCs as they mature from Retics. Our hypothesis that rafts serve as additional anchoring sites for the lipid bilayer to the underlying membrane-skeleton is corroborated by the present results. It is becoming ever more clear that a proper lipid composition of the reticulocyte is necessary for the production of a normal mature RBC.

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The Shape Shifting Story of Reticulocyte Maturation

Cited by 54 publications

References 159 publications

Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

A conserved requirement forFbxo7during male germ cell cytoplasmic remodelling

Membrane Rearrangements in the Maturation of Circulating Human Reticulocytes

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