The erythrocyte membrane has proven to be an accessible and informative membrane system. The existence of related proteins in nonerythroid membranes attests to the general relevance of this model. Also, specific molecular defects have been identified which result in clinical anemias. The long term goals of this proposal are to explore the normal and pathological roles of two very recently identified integral membrane proteins and to evaluate variants of recognized membrane proteins found in certain congenital anemias. I. The clinically important Rh antigen system will be investigated at a molecular level by focusing upon the 30,000 Mr Rh associated integral membrane protein (Rh-IMP). Rh-IMPs purified from blood with specific Rh types will be analyzed for intrinsic differences in peptide composition. The importance of the covalent fatty acylations will be studied. Associations with other proteins and details of the specific membrane conformation required for surface immunogenicity will be investigated. II. The 28,000 Mr membrane-skeleton-linked integral membrane protein will be studied. The physical and chemical nature of the protein, the existence in nonerythroid cells, nature of the membrane-skeleton linkage, and potential physiologic functions will be investigated. III. The roles of protein 4.1 and spectrin will be analyzed in certain congenital anemias. The prevalence of 4.1 variants in ovalocytosis will be ascertained, and functional consequences of recently identified 4.1 variants will be measured. The role of spectrin in spherocytosis will be further evaluated.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Rash, J E (2010) Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system. Neuroscience 168:982-1008
Huang, Chunyi George; Lamitina, Todd; Agre, Peter et al. (2007) Functional analysis of the aquaporin gene family in Caenorhabditis elegans. Am J Physiol Cell Physiol 292:C1867-73
Liu, Kun; Nagase, Hiroaki; Huang, Chunyi George et al. (2006) Purification and functional characterization of aquaporin-8. Biol Cell 98:153-61
Huang, Chunyi George; Agre, Peter; Strange, Kevin et al. (2006) Isolation of C. elegans deletion mutants following ENU mutagenesis and thermostable restriction enzyme PCR screening. Mol Biotechnol 32:83-6
Beitz, Eric; Liu, Kun; Ikeda, Masahiro et al. (2006) Determinants of AQP6 trafficking to intracellular sites versus the plasma membrane in transfected mammalian cells. Biol Cell 98:101-9
Liu, Zijuan; Carbrey, Jennifer M; Agre, Peter et al. (2004) Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem Biophys Res Commun 316:1178-85
Preston, Gregory M (2003) Cloning gene family members using PCR with degenerate oligonucleotide primers. Methods Mol Biol 226:485-98
Hazama, Akihiro; Kozono, David; Guggino, William B et al. (2002) Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation. J Biol Chem 277:29224-30
Nejsum, Lene N; Kwon, Tae-Hwan; Jensen, Uffe B et al. (2002) Functional requirement of aquaporin-5 in plasma membranes of sweat glands. Proc Natl Acad Sci U S A 99:511-6
Engel, Andreas; Stahlberg, Henning (2002) Aquaglyceroporins: channel proteins with a conserved core, multiple functions, and variable surfaces. Int Rev Cytol 215:75-104

Showing the most recent 10 out of 86 publications