The shape of the vertebrate lens is determined in part by a morphogenetic program in which dramatic changes in the actin and intermediate filament cytosekeletal network occur. An important component of this network is the lens fiber cell specific intermediate filaments, called the beaded filaments. The long-term objective of the research is to understand how the cytoskeletal components are integrated to accomplish the morphogenetic changes that occur during development and how these confer the lens' unique optical functions. The proposal seeks to determine: (1) how tropomodulin (Tmod), an actin filament capping protein that is upregulated during lens differentiation, actin and the beaded filaments are organized during development in the embryonic chick lens; (2) to determine biochemical and ultrastructural characteristics of the interactions between Tmod and actin and beaded filaments; (3) to elucidate the functional significance of the interactions between Tmod and these other cytoskeletal components. These goals will be accomplished using a combination of state of the art molecular, biochemical and microscopic techniques. The results of the work should provide a link between the biochemical characteristics of cytoskeletal assembly and lens morphology and have implications for the role of the cytoskeleton in lens fiber cell differentiation and cataract formation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY010814-06A1
Application #
6202886
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1995-01-01
Project End
2004-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
6
Fiscal Year
2000
Total Cost
$292,468
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Nowak, Roberta B; Fischer, Robert S; Zoltoski, Rebecca K et al. (2009) Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens. J Cell Biol 186:915-28
Fischer, R S; Quinlan, R A; Fowler, V M (2003) Tropomodulin binds to filensin intermediate filaments. FEBS Lett 547:228-32
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
Lee, A; Morrow, J S; Fowler, V M (2001) Caspase remodeling of the spectrin membrane skeleton during lens development and aging. J Biol Chem 276:20735-42
Fischer, R S; Lee, A; Fowler, V M (2000) Tropomodulin and tropomyosin mediate lens cell actin cytoskeleton reorganization in vitro. Invest Ophthalmol Vis Sci 41:166-74
Lee, A; Fischer, R S; Fowler, V M (2000) Stabilization and remodeling of the membrane skeleton during lens fiber cell differentiation and maturation. Dev Dyn 217:257-70
Woo, M K; Lee, A; Fischer, R S et al. (2000) The lens membrane skeleton contains structures preferentially enriched in spectrin-actin or tropomodulin-actin complexes. Cell Motil Cytoskeleton 46:257-68
Almenar-Queralt, A; Lee, A; Conley, C A et al. (1999) Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle. J Biol Chem 274:28466-75
Littlefield, R; Fowler, V M (1998) Defining actin filament length in striated muscle: rulers and caps or dynamic stability? Annu Rev Cell Dev Biol 14:487-525
Fowler, V M (1997) Capping actin filament growth: tropomodulin in muscle and nonmuscle cells. Soc Gen Physiol Ser 52:79-89

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