The Proteome of the Red Blood Cell: An Auspicious Source of New Insights into Membrane-Centered Regulation of Homeostasis

Abstract

During the past decade, the hand-in-hand development of biotechnology and bioinformatics has enabled a view of the function of the red blood cell that surpasses the supply of oxygen and removal of carbon dioxide. Comparative proteomic inventories have yielded new clues to the processes that regulate membrane–cytoskeleton interactions in health and disease, and to the ways by which red blood cells communicate with their environment. In addition, proteomic data have revealed the possibility that many, hitherto unsuspected, metabolic processes are active in the red blood cell cytoplasm. Recent metabolomic studies have confirmed and expanded this notion. Taken together, the presently available data point towards the red blood cell membrane as the hub at which all regulatory processes come together. Thus, alterations in the association of regulatory proteins with the cell membrane may be a sine qua non for the functional relevance of any postulated molecular mechanism. From this perspective, comparative proteomics centered on the red blood cell membrane constitute a powerful tool for the identification and elucidation of the physiologically and pathologically relevant pathways that regulate red blood cell homeostasis. Additionally, this perspective provides a focus for the interpretation of metabolomic studies, especially in the development of biomarkers in the blood.

Disturbed Red Blood Cell Structure and Function: An Exploration of the Role of Red Blood Cells in Neurodegeneration

“…Physiological aging in vivo , as well as aging in vitro during storage in the blood bank, induces changes in the red cell membrane ( 7 ), in the activity of the main metabolic pathways ( 8 , 9 ), and in hemoglobin ( 10 ). These changes not only affect function by decreasing deformability ( 11 , 12 ), but also lead to the appearance of signals that trigger recognition and removal by the immune system.…”

Red Blood Cell Homeostasis: Mechanisms and Effects of Microvesicle Generation in Health and Disease

“…Increased vesiculation is associated with systemic inflammation, which may be directly responsible for hemolysis and anemia ( Dinkla et al, 2012b , 2016 ). Thus, microvesicles are part of the complex of interactions between RBCs and the organism ( Bosman, 2016a , b ). In this review, we aim to integrate the newest data on microvesicle composition and production in various conditions, in order to obtain more insight into the basic mechanisms underlying microvesicle generation, and the involvement of RBC-derived microvesicles in pathophysiology.…”

Blood Cell Proteomics in Chronic Kidney Disease

“…A recent, in depth quantitative analysis of the RBC proteome, identified 2650 proteins, 1890 of them occurring at more than 100 copies per cell, findings which were validated by a targeted analysis using labelled standards and which can serve as a useful tool for further studies on RBC pathologies and aging [30]. Comparative proteomic inventories of RBC membrane have yielded new clues to the mechanisms regulating membrane-cytoskeleton interactions in health and disease, and to the ways by which erythrocytes communicate with their environment [31]. In addition, proteomic data have indicated that many, hitherto unsuspected, metabolic processes may be active in the RBC cytoplasm [31], as suggested by the presence of new receptor/signaling pathways, stress proteins, transport systems, and proteases [28,32].…”

“…Comparative proteomic inventories of RBC membrane have yielded new clues to the mechanisms regulating membrane-cytoskeleton interactions in health and disease, and to the ways by which erythrocytes communicate with their environment [31]. In addition, proteomic data have indicated that many, hitherto unsuspected, metabolic processes may be active in the RBC cytoplasm [31], as suggested by the presence of new receptor/signaling pathways, stress proteins, transport systems, and proteases [28,32]. Interestingly, erythrocyte metabolism does not seem to be restricted to energy production and redox status, since amino acid and lipid metabolism may be particularly active as well [33,34].…”