Determinants of erythrocyte hydration

Abstract

Purpose of review: Maintenance of cellular water and solute homeostasis is critical for survival of the erythrocyte. Inherited or acquired disorders that perturb this homeostasis jeopardize the erythrocyte, leading to its premature destruction. This study reviews recent progress in our understanding the determinants of erythrocyte hydration and its related disorders.

Recent findings: The molecular and genetic bases of primary disorders of erythrocyte hydration are poorly understood. Recent studies have implicated roles for the anion transporter, SLC4A1, and the Rh-associated glycoprotein, RhAG. The most common secondary disorder associated with perturbed hydration of the erythrocyte is sickle cell disease, in which dehydration contributes to disease pathology and clinical complications. Advances in understanding the mechanisms regulating erythrocyte solute and water content, particularly associated with KCl cotransport and Gardos channel activation, have revealed novel signaling mechanisms controlling erythrocyte hydration. These signaling pathways may provide innovative strategies to prevent erythrocyte dehydration in sickle cell disease.

Summary: Clinical, translational and biologic studies all contribute to our knowledge of erythrocyte hydration. Understanding the mechanisms controlling erythrocyte water and solute homeostasis will serve as a paradigm for other cells and may reveal new therapeutic targets for disease prevention and treatment.

Figure 1. A partial model of band 3, the erythrocyte membrane anion transporter

Transmembrane domains seven through twelve, shaded gray, and intracellular and extracellular loops, shaded white, are shown. Missense mutations in this region associated with ablation of anion function and abnormal cation leak, shaded black, are labeled.

Figure 2. Proteomic workflows for identification and quantitation of phosphorylated proteins and peptides

Workflow is divided into two options: one for TiO₂ enrichment of phosphopeptides after the protein(s) of interest are purified or immunoprecipitated and another for more complex phosphopeptide mixtures directly extracted from tissue or whole cell extracts. The former is a more targeted approach to discover numerous sites of phosphorylation on proteins of interest, whereas the latter is directed towards more global discovery based approaches. For most of these approaches, three different quantitative methods (SILAC, iTRAQ, and label-free quantitation) can be introduced at steps indicated by “Q” to determine changes of phosphorylation between two or more samples.