Date of Award

11-5-2002

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Katherine A Sukalski

Abstract

Interactions between the glycolytic enzymes lactate dehydrogenase A (LDHA), lactate dehydrogenase B (LDHB) and aldolase and F-actin o f the cytoskeleton were studied by constructing enzyme/GFP (green fluorescent protein) fusion proteins and measuring the interactions via in vitro co-precipitation analysis and in vivo localization analysis using fluorescent and confocal microscopy. Primers were used to isolate the genes o f LDHA, LDHB and aldolase from human muscle and heart cDNA libraries by PCR. GFP-fusion proteins were designed in N-terminal and C-terminal directions. GFPfusion proteins containing the 10-terminal amino acids from both the N and C terminus o f these enzymes were also prepared. Bacterial fusions that were used in co-precipitation experiments interacted with mammalian F-actin with the same affinity as GFP except for C-terminal GFP-aldolase, which expressed 3X the binding o f the other constructs. Eukaryotic fusions were expressed in 3T3 cells and localization o f LDHA, LDHB, aldolase and the peptide fusions within these cells, determined by microscopy. GFP and the constructed fusion proteins appeared to associate with F-actin along stress fibers within these cells.

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