Endocytosis is a fundamental biological process that is involved in numerous cellular functions including receptor cycling, metabolism and the entry of assorted macromolecules into the cell. Even though the process is highly regulated, the factors that direct the different macromolecules from the outside of the cell to their target sites in the cell are not well understood. Polypeptide motifs may be crucial in steering different proteins to different cellular compartments and/or different vesicles that comprise the endocytic pathway.
The aim of this project is to characterize the endocytic pathway in cardiac myocytes, to identify specific peptide motifs that target endocytosis into cardiac myocytes as well as to define the pathways by which each mediates endocytosis, and to determine the role of Caveolin-3 (cav-3) in cardiac myocyte endocytosis. The methods will involve i) colocalization studies using fluorescent probes, ii) peptide and antibody phage display and bactria-based peptide display biopanning, iii) the study of cav-3 knockout mice. The discoverry of polypeptides that guide macromolecules to specific cellular organelles or compartments can have profound implications for understanding microbial invasion and for refining gene therapy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL076016-01
Application #
6738692
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Commarato, Michael
Project Start
2004-01-01
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
1
Fiscal Year
2004
Total Cost
$58,336
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Ziello, Jennifer E; Huang, Yan; Jovin, Ion S (2010) Cellular endocytosis and gene delivery. Mol Med 16:222-9
Ziello, Jennifer E; Jovin, Ion S; Huang, Yan (2007) Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med 80:51-60