Actin-capping proteins which bind to the barbed ends of actin filaments have been isolated from a variety of non-muscle tissues. We have recently purified such a protein from skeletal muscle. The purpose of this proposal is to take advantage of the unique structure/function relationships of muscle proteins to help define the biological role of this and other actin-capping proteins. We plan to do this by: 1) developing monoclonal and polyclonal antibodies which specifically recognize the capping protein 2) using techniques of indirect immunofluorescence and immunoelectron microscopy to localize the capping protein in muscle and non-muscle tissues 3) identifying and purifying proteins which demonstrate physiological protein-protein interactions with the capping protein and studying their binding to the capping protein in solution and extracted tissues 4) studying the localization of the capping protein during embryogenesis in chick myocardium. Our short term goal will be to explore the possibility that capping proteins may be responsible for mediating the attachment of actin filaments to structures such as the Z-line of skeletal muscle. The long term goal of this proposal is to develop an understanding of how the length, number, and attachments of actin filaments to other structures are regulated.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038855-02
Application #
3471354
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1987-09-30
Project End
1992-09-29
Budget Start
1988-09-30
Budget End
1989-09-29
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Frontini, Maria G; Srinivasan, Sathanur R; Xu, Jihua et al. (2008) Usefulness of childhood non-high density lipoprotein cholesterol levels versus other lipoprotein measures in predicting adult subclinical atherosclerosis: the Bogalusa Heart Study. Pediatrics 121:924-9
Srinivasan, Sathanur R; Frontini, Maria G; Xu, Jihua et al. (2006) Utility of childhood non-high-density lipoprotein cholesterol levels in predicting adult dyslipidemia and other cardiovascular risks: the Bogalusa Heart Study. Pediatrics 118:201-6
Srinivasan, Sathanur R; Myers, Leann; Berenson, Gerald S (2002) Distribution and correlates of non-high-density lipoprotein cholesterol in children: the Bogalusa Heart Study. Pediatrics 110:e29
Casella, J F; Barron-Casella, E A; Torres, M A (1995) Quantitation of Cap Z in conventional actin preparations and methods for further purification of actin. Cell Motil Cytoskeleton 30:164-70
Casella, J F; Torres, M A (1994) Interaction of Cap Z with actin. The NH2-terminal domains of the alpha 1 and beta subunits are not required for actin capping, and alpha 1 beta and alpha 2 beta heterodimers bind differentially to actin. J Biol Chem 269:6992-8
Hug, C; Miller, T M; Torres, M A et al. (1992) Identification and characterization of an actin-binding site of CapZ. J Cell Biol 116:923-31
Casella, J F; Cooper, J A (1991) Purification of cap Z from chicken skeletal muscle. Methods Enzymol 196:140-54
Casella, J F; Casella, S J; Hollands, J A et al. (1989) Isolation and characterization of cDNA encoding the alpha subunit of Cap Z(36/32), an actin-capping protein from the Z line of skeletal muscle. Proc Natl Acad Sci U S A 86:5800-4
Caldwell, J E; Waddle, J A; Cooper, J A et al. (1989) cDNAs encoding the beta subunit of cap Z, the actin-capping protein of the Z line of muscle. J Biol Chem 264:12648-52