Abstract

Membrane structure and function provide for the requisite import and export of required macromolecules, receptor-mediated cell signaling, and, of course, for cell integrity as well the compartmentalization of proteins and nucleic acids. Recent evidence indicates that moonlighting GAPDH fulfills important roles in both membrane structure and function. This includes its requirement for membrane fusion and for basic mechanisms of receptor-mediated iron metabolism. The former may be required for nuclear membrane fusion as a penultimate step in cell division. The latter includes not only iron import and its intracellular transport but also its extracellular acquisition. Each function may involve individual GAPDH isozymes as well as a specific phosphatidylserine binding site within its NAD+ domain. In toto, these findings highlight the interrelationship between membrane function and moonlighting GAPDH activity.

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