Anemia Research Today is a free monthly online journal that collates and summarizes the latest research about Anemia, including details on symptoms, diagnosis, diet, treatment, causes.

Protein-4.2 association with band 3 (AE1, SLCA4) in Xenopus oocytes: effects of three natural protein-4.2 mutations associated with hemolytic anemia.

Toye AM, Ghosh S, Young MT, Jones GK, Sessions RB, Ramaugé M, Leclerc P, Basu J, Delaunay J, Tanner MJ

Department of Biochemistry, School of Medical Sciences, University of Bristol, BS8 1TD, United Kingdom. ash.m.toye@bristol.ac.uk

We have investigated the effects of coexpression of protein 4.2 and three protein-4.2 variants with band 3 in the Xenopus oocyte expression system. Normal protein 4.2 increased band-3-specific chloride transport in the oocytes. Protein 4.2 also coimmunoprecipitated with band 3 and colocalized with band 3 at the oocyte plasma membrane. The increase in band-3-mediated chloride transport and coimmunoprecipitation of protein 4.2 required the presence of the N-terminal cytoplasmic domain of band 3. Protein 4.2 also localized to the oocyte plasma membrane in the absence of band 3. The protein-4.2 variants 4.2 Tozeur (R310Q) and 4.2 Komatsu (D175Y) had impaired ability to bind to band 3 and these variants did not localize to the oocyte plasma membrane when expressed on their own or when coexpressed with band 3. Unexpectedly, 4.2 Nippon (A142T) behaved similarly to normal protein 4.2. In the absence of a crystal structure of protein 4.2, we propose a homology model of protein 4.2 based on the structure of the sequence-related protein transglutaminase. Using our results in oocytes and this homology model we speculate how these mutations affect protein 4.2 and result in hereditary spherocytosis.

Published 3 May 2005 in Blood, 105(10): 4088-95.
Full-text of this article is available online (may require subscription).

© 2004-2008 Anemia Research Today. All Rights Reserved.