Abstract

The role of the protein spectrin in evaluating human erythrocyte surface macromolecule mobility and topography will be investigated. To determine how spectrin regulates the distribution of other membrane proteins, the binding of spectrin to the inside surface of spectrin depleted native membranes and to the surface of protein-lipid recombinants will be examined with the aim of isolating the binding site(s) and evaluating the binding affinities under differing physiochemical conditions. To measure the control spectrin exerts on other membrane components, fluorescence bleaching and free-fracture electron microscopy following fusion will be used to evaluate how the molecular associations of spectrin actually influence macromolecule mobility and topography. It is expected that this detailed examination of the structure and associative properties of the spectrin molecule will provide a firm basis for understanding several pathological syndromes of the red cell which have been traced to perturbations in the organization of its membrane.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL017411-17
Application #
3335358
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1977-12-01
Project End
1992-11-30
Budget Start
1990-12-15
Budget End
1991-11-30
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Bjorkoy, A; Mikkelsen, A; Elgsaeter, A (1999) Electric birefringence of recombinant spectrin segments 14, 14-15, 14-16, and 14-17 from Drosophila alpha-spectrin. Biochim Biophys Acta 1430:323-40
Takei, K; Chan, T A; Wang, F S et al. (1999) The neural cell adhesion molecules L1 and NCAM-180 act in different steps of neurite outgrowth. J Neurosci 19:9469-79
Bjorkoy, A; Elgsaeter, A; Mikkelsen, A (1998) Electrooptic analysis of macromolecule dipole moments using asymmetric reversing electric pulses. Biophys Chem 72:247-64
Ralston, G; Cronin, T; Branton, D (1996) Self-association of spectrin's repeating segments. Biochemistry 35:5257-63
Marfatia, S M; Leu, R A; Branton, D et al. (1995) Identification of the protein 4.1 binding interface on glycophorin C and p55, a homologue of the Drosophila discs-large tumor suppressor protein. J Biol Chem 270:715-9
Dahl, S C; Geib, R W; Fox, M T et al. (1994) Rapid capping in alpha-spectrin-deficient MEL cells from mice afflicted with hereditary hemolytic anemia. J Cell Biol 125:1057-65
Viel, A; Branton, D (1994) Interchain binding at the tail end of the Drosophila spectrin molecule. Proc Natl Acad Sci U S A 91:10839-43
Marfatia, S M; Lue, R A; Branton, D et al. (1994) In vitro binding studies suggest a membrane-associated complex between erythroid p55, protein 4.1, and glycophorin C. J Biol Chem 269:8631-4
Lue, R A; Marfatia, S M; Branton, D et al. (1994) Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1. Proc Natl Acad Sci U S A 91:9818-22
Yan, Y; Winograd, E; Viel, A et al. (1993) Crystal structure of the repetitive segments of spectrin. Science 262:2027-30

Showing the most recent 10 out of 24 publications