Timothy J Satchwell, Amanda J Bell, Bethan R Hawley, Stephanie Pellegrin, Kathryn E Mordue, Cees Th B M van Deursen, Nicole Heitink-Ter Braak, Gerwin Huls, Mathie P G Leers, Eline Overwater, Rienk Y J Tamminga, Bert van der Zwaag, Elisa Fermo, Paola Bianchi, Richard van Wijk, Ashley M Toye
Ankyrin-R provides a key link between band 3 and the spectrin cytoskeleton that helps to maintain the highly specialized erythrocyte biconcave shape. Ankyrin deficiency results in fragile spherocytic erythrocytes with reduced band 3 and protein 4.2 expression. We use in vitro differentiation of erythroblasts transduced with shRNAs targeting ANK1 to generate erythroblasts and reticulocytes with a novel ankyrin-R 'near null' human phenotype with less than 5% of normal ankyrin expression. Using this model, we demonstrate that absence of ankyrin negatively impacts the reticulocyte expression of a variety of proteins, including band 3, glycophorin A, spectrin, adducin and, more strikingly, protein 4...
September 2016: Haematologica