Caveolin-1 A scaffold for microcompartmental organization of membrane-associated glycolysis

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The role of membrane caveolae in the compartmentation of membrane glycolytic metabolism indicates a pivotal role of caveolin in the localization of glycolytic enzymes to this membrane domain. This dissertation demonstrates the following about the role of protein scaffold caveolin-1 (CAV-1) in the compartmentation of membrane glycolytic metabolism. 1) CAV-1 a scaffold of phosphofructokinase (PFK) can also target other glycolytic enzymes such as aldolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and pyruvate kinase (PK) to the membrane of lymphocytes transfected with caveolin-1 (CAV-1). 2) CAV-1 is subject to regulation during enhanced glycolytic metabolism in astrocytes after 24 hour exposure to high NH4Cl. 3) The caveolin-1 scaffolding domain (CSD) is essential for the targeting of glycolytic enzyme PFK to the cell membrane in the vascular smooth muscle cell line A7r5. This dissertation addressed these three fundamental roles of caveolin-1 that support the essential role of caveolins in the organization of membrane associated glycolytic metabolism.