Molecular biology of Rh proteins and relevance to molecular medicine

Abstract

The Rhesus (Rh) blood group system is expressed by a pair of 12-transmembrane-domain-containing proteins, the RhCcEe and RhD proteins. RhCcEe and RhD associate as a Rh core complex that comprises one RhD/CcEe protein and most likely two Rh-associated glycoproteins (RhAG) as a trimer. All these Rh proteins are homologous and share this homology with two human non-erythroid proteins, RhBG and RhCG. All Rh protein superfamily members share homology and function in a similar manner to the Mep/Amt ammonium transporters, which are highly conserved in bacteria, plants and invertebrates. Significant advances have been made in our understanding of the structure and function of Rh proteins, as well as in the clinical management of Rh haemolytic disease. This review summarises our current knowledge concerning the molecular biology of Rh proteins and their role in transfusion and pregnancy incompatibility.

Nitrogen excretion in developing zebrafish (Danio rerio): a role for Rh proteins and urea transporters

“…In mammals, Rhag is almost exclusively found on the red blood cell and appears to play a vital role in maintaining its structural integrity (2). Mutants lacking a functional Rhag protein display the Rh null phenotype and suffer both structural and biochemical abnormalities of the red blood cell, resulting in chronic hemolytic anemia (7,17,21).…”

“…"Acid trapping", acidification of the gill boundary layer via hydration of CO 2 or direct excretion of protons, results in the conversion of excreted NH 3 into NH 4 ϩ , thereby maintaining a favorable gradient for NH 3 movement (43,55,59).…”

Immunoproteomics: From biomarker discovery to diagnostic applications

“…Examples of autoimmune diseases include rheumatoid arthritis (RA), autoimmune type I diabetes, psoriasis and systemic lupus erythematosus (SLE), in which a variety of self-components are targeted by IgG or IgM antibodies [62,63]. In addition, autoimmune-like diseases can occur during blood transfusions or pregnancy when antirhesus antibodies are formed that target the red blood cells from the donor or foetus, respectively [64]. Moreover, an autoimmune reaction towards placental components has been implicated in the development of preeclampsia [65], which is a life-threatening situation for pregnant women.…”

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

“…15,17 The Rh-band 3 complex includes the RhAG2-Rh protein trimer, 27,28 CD47, ICAM-4 and band 3 dimers/tetramers. 29,30 Red cell turnover accounts for the highly regulated processing of approximately 10 12 effete red cells per day. This is governed by a process termed eryptosis, 31 which has several functional differences to apoptosis.…”