The membrane of the human red cell has been embraced by cell biologists as a simple model with direct relevance to the complex membranes of non-erythroid cells. While the structural biology of the ankyrin-band 3 end of the spectrin cytoskeleton have been thoroughly studied, the opposite end of the spectrin cytoskeleton has remained puzzling and has proven to be a complex of multiple polypeptides. The applicant proposes to elucidate the molecular determinants of actin filament length in red cells and certain muscle cells. Addition and removal of actin from the barbed ends of filaments has been studied extensively, but the determinants of pointed end growth are not well understood. Previous work by this applicant led to the identification and characterization of tropomodulin in red cells. In the presence of tropomyosin, tropomodulin was shown to cap the pointed ends of actin filaments. The investigator proposes a series of cellular and molecular biological studies to further explain this process. She plans to map the filament and pointed end binding domains on tropomodulin and explore the contributions of tropomyosin to this association. Using cultured cardiac and skeletal myogenic cells, she will examine the effects of varying tropomodulin concentrations and will attempt to block specific domains with injected antibodies. She will search for and characterize new non-erythroid tropomodulin isoforms. The roles of adducing, eCP, and tropomodulin will be evaluated by mechanically stressing red cell membranes.
| Smith, Alyson S; Nowak, Roberta B; Zhou, Sitong et al. (2018) Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability. Proc Natl Acad Sci U S A 115:E4377-E4385 |
| Fath, Thomas; Fischer, Robert S; Dehmelt, Leif et al. (2011) Tropomodulins are negative regulators of neurite outgrowth. Eur J Cell Biol 90:291-300 |
| Weber, Kari L; Fischer, Robert S; Fowler, Velia M (2007) Tmod3 regulates polarized epithelial cell morphology. J Cell Sci 120:3625-32 |
| Fischer, Robert S; Yarmola, Elena G; Weber, Kari L et al. (2006) Tropomodulin 3 binds to actin monomers. J Biol Chem 281:36454-65 |
| Gupton, Stephanie L; Anderson, Karen L; Kole, Thomas P et al. (2005) Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin. J Cell Biol 168:619-31 |
| Ehler, Elisabeth; Fowler, Velia M; Perriard, Jean-Claude (2004) Myofibrillogenesis in the developing chicken heart: role of actin isoforms and of the pointed end actin capping protein tropomodulin during thin filament assembly. Dev Dyn 229:745-55 |
| Fowler, Velia M; Greenfield, Norma J; Moyer, Jeannette (2003) Tropomodulin contains two actin filament pointed end-capping domains. J Biol Chem 278:40000-9 |
| Fritz-Six, Kimberly L; Cox, Patrick R; Fischer, Robert S et al. (2003) Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality. J Cell Biol 163:1033-44 |
| Fischer, Robert S; Fowler, Velia M (2003) Tropomodulins: life at the slow end. Trends Cell Biol 13:593-601 |
| Fischer, Robert S; Fritz-Six, Kimberly L; Fowler, Velia M (2003) Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility. J Cell Biol 161:371-80 |
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