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Erythrocyte membrane proteins and their diseases: introduction
Seminars in
HEMATOLOGY Vol 41, No 2, April 2004
Erythrocyte Membrane Proteins and Their Diseases: Introduction Narla Mohandas
D
R WATER GRATZER’S comment in Nature a decade ago that the “Red cell is more Red than Dead” continues to be highly relevant as evidenced by the five articles on “Erythrocyte Membrane Proteins and Their Diseases” in this issue of Seminars in Hematology. The last time this subject was reviewed in Seminars was in 1993, when Dr Jiri Palek made an extraordinary compilation of the state of the art of this field as it existed then. In the intervening years, as outlined here, substantial progress has been made in our understanding of the role of the many erythrocyte proteins in regulating normal and pathologic features of red cell membrane physiology. The first contribution to this issue is an article on red blood cell blood group antigens that reviews our current understanding of the structure and function of these important surface molecules. Since 1993, the molecular structure of all blood group antigens has been defined and the function of a significant number has been delineated. Substantial progress in this area was recognzied by Nobel Committee, who awarded Dr Peter Agre the Chemistry Prize in 2003 for describing the function of the Colton blood group antigen as a red cell water channel. The second article is a comprehensive discussion of the various molecular defects that result in the most common red cell membrane disorder, hereditary spherocytosis, as well as detailed treatment of the pathophysiology of this disorder. We now have a relatively full understanding of this important hematologic disease at the cellular, biochemical, and molecular levels. The third contribution describes the various defects that produce hereditary elliptocytosis. The most common molecular lesions in this red cell phenotype involve mutations in spectrin genes; mutations in genes
encoding protein 4.1R and glycophorin C can also produce hereditary elliptocytosis. Clinical manifestations and management of both hereditary spherocytosis and hereditary elliptocytosis are also provided by leading world experts in these diseases. The fourth review explores genetic disorders affecting red cell membrane permeability to monovalent cations. Significant progress has been made during the last decade in the phenotypic description of red cell membrane permeability defects in this heterogenous group of disorders. However, we are far from defining the responsible molecular sites. The finding of a significant incidence of post-splenectomy thrombotic events in a number of patients with cation permeability defects is of great clinical importance and needs to be addressed critically. The final contribution explores membrane alterations induced by the malarial parasite, Plasmodium falciparum, in the infected red cell. The sequencing and annotation of the complete genome of the parasite, as well as the development of the proteomic profiles of the parasite, have opened up new areas of investigation into how parasites modify host red cells for their benefit. This exciting area is in a nascent stage of development. These five review articles in the current issue of Seminars in Hematology attest to the enormous progress made during the last decade in our understanding of the contribution of red cell membrane proteins to human From the New York Blood Center, New York, NY. Address correspondence to Narla Mohandas, DSc, 310 E 67th St, New York, NY 10021. © 2004 Elsevier Inc. All rights reserved. 0037-1963/04/4102-0007$30.00/0 doi:10.1053/j.seminhematol.2004.03.001
Seminars in Hematology, Vol 41, No 2 (April), 2004: pp 91-92
91
92
Narla Mohandas
diseases. While we can all take pride in this progress we need to remind ourselves of the large number of remaining gaps in our understanding. For example, the function of a number of important red cell surface molecules, such as the Rh proteins, still needs to be defined. The role of red cells in thrombosis is a novel area of investigation that that also requires active exploration. Finally, our understanding of how the malarial parasite
commandeers the red cell for its survival is still very rudimentary. As malarial infections continue to be a major public health problem on a global scale, hematology investigators should energetically and creatively address this important red cell problem. It is my fond hope that the next Seminars issue dedicated to red cell membrane proteins and their diseases will describe exciting advances in these areas!
HEMATOLOGY Vol 41, No 2, April 2004
Erythrocyte Membrane Proteins and Their Diseases: Introduction Narla Mohandas
D
R WATER GRATZER’S comment in Nature a decade ago that the “Red cell is more Red than Dead” continues to be highly relevant as evidenced by the five articles on “Erythrocyte Membrane Proteins and Their Diseases” in this issue of Seminars in Hematology. The last time this subject was reviewed in Seminars was in 1993, when Dr Jiri Palek made an extraordinary compilation of the state of the art of this field as it existed then. In the intervening years, as outlined here, substantial progress has been made in our understanding of the role of the many erythrocyte proteins in regulating normal and pathologic features of red cell membrane physiology. The first contribution to this issue is an article on red blood cell blood group antigens that reviews our current understanding of the structure and function of these important surface molecules. Since 1993, the molecular structure of all blood group antigens has been defined and the function of a significant number has been delineated. Substantial progress in this area was recognzied by Nobel Committee, who awarded Dr Peter Agre the Chemistry Prize in 2003 for describing the function of the Colton blood group antigen as a red cell water channel. The second article is a comprehensive discussion of the various molecular defects that result in the most common red cell membrane disorder, hereditary spherocytosis, as well as detailed treatment of the pathophysiology of this disorder. We now have a relatively full understanding of this important hematologic disease at the cellular, biochemical, and molecular levels. The third contribution describes the various defects that produce hereditary elliptocytosis. The most common molecular lesions in this red cell phenotype involve mutations in spectrin genes; mutations in genes
encoding protein 4.1R and glycophorin C can also produce hereditary elliptocytosis. Clinical manifestations and management of both hereditary spherocytosis and hereditary elliptocytosis are also provided by leading world experts in these diseases. The fourth review explores genetic disorders affecting red cell membrane permeability to monovalent cations. Significant progress has been made during the last decade in the phenotypic description of red cell membrane permeability defects in this heterogenous group of disorders. However, we are far from defining the responsible molecular sites. The finding of a significant incidence of post-splenectomy thrombotic events in a number of patients with cation permeability defects is of great clinical importance and needs to be addressed critically. The final contribution explores membrane alterations induced by the malarial parasite, Plasmodium falciparum, in the infected red cell. The sequencing and annotation of the complete genome of the parasite, as well as the development of the proteomic profiles of the parasite, have opened up new areas of investigation into how parasites modify host red cells for their benefit. This exciting area is in a nascent stage of development. These five review articles in the current issue of Seminars in Hematology attest to the enormous progress made during the last decade in our understanding of the contribution of red cell membrane proteins to human From the New York Blood Center, New York, NY. Address correspondence to Narla Mohandas, DSc, 310 E 67th St, New York, NY 10021. © 2004 Elsevier Inc. All rights reserved. 0037-1963/04/4102-0007$30.00/0 doi:10.1053/j.seminhematol.2004.03.001
Seminars in Hematology, Vol 41, No 2 (April), 2004: pp 91-92
91
92
Narla Mohandas
diseases. While we can all take pride in this progress we need to remind ourselves of the large number of remaining gaps in our understanding. For example, the function of a number of important red cell surface molecules, such as the Rh proteins, still needs to be defined. The role of red cells in thrombosis is a novel area of investigation that that also requires active exploration. Finally, our understanding of how the malarial parasite
commandeers the red cell for its survival is still very rudimentary. As malarial infections continue to be a major public health problem on a global scale, hematology investigators should energetically and creatively address this important red cell problem. It is my fond hope that the next Seminars issue dedicated to red cell membrane proteins and their diseases will describe exciting advances in these areas!