Dematin key to erythrocyte membrane stability in mice

Can these findings in the erythrocytes of genetically altered mice be extrapolated to humans?

While similar, membrane composition differs in mouse and human erythrocytes. The junctional complex contains Rh polypeptides in mice but does not in humans. Glucose transporter 1 (Glut1), which associates with dematin and the adducins in humans, is not expressed in the mature erythrocytes of mice. The authors propose a model in which adducin stabilized by dematin provides linkage to the plasma membrane via band 3; however, the relatively mild phenotype seen in the alpha adducin knockout mouse argues for additional linkages, likely via dematin.

It will be important to determine the role of dematin and the effect of its deficiency in junctional complex assembly, in regulation of membrane deformability and stability in human erythrocytes, and in the context of its identified association with Glut1. Given the importance of phosphorylation in regulation of dematin-binding function and interactions, and in light of the gross disruptive effects of dematin absence reported in the study by Ms. Lu and her colleagues, investigation of the role of dematin modification in junctional protein complex assembly, enucleation and cytoskeletal remodeling, and response to malaria invasion of the red blood cell will all represent important areas of future research.

Timothy J. Satchwell, PhD, and Ashley M. Toye, PhD, of the University of Bristol, England, made their comments in an accompanying editorial (Blood. 2016;128:11-12).