Subcellular dynamics of multifunctional protein regulation: mechanisms of GAPDH intracellular translocation

Abstract

Multidimensional proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibit distinct activities unrelated to their originally identified functions. Apart from glycolysis, GAPDH participates in iron metabolism, membrane trafficking, histone biosynthesis, the maintenance of DNA integrity and receptor mediated cell signaling. Further, multifunctional proteins exhibit distinct changes in their subcellular localization reflecting their new activities. As such, GAPDH is not only a cytosolic protein but is localized in the membrane, the nucleus, polysomes, the ER and the Golgi. In addition, although the initial subcellular localizations of multifunctional proteins may be of significance, dynamic changes in intracellular distribution may occur as a consequence of those new activities. As such, regulatory mechanisms may exist through which cells control multifunctional protein expression as a function of their subcellular localization. The temporal sequence through which subcellular translocation and the acquisition of new GAPDH functions is considered as well as post-translational modification as a basis for its intracellular transport.

Figure I. Subcellular GAPDH Dynamics

Figure II. Constitutive GAPDH Translocation

Figure III. GAPDH and the Maintenance of DNA Integrity

Figure IV. Inducible GAPDH Translocation

Figure V. GAPDH and Receptor Mediated Cell Signaling

Figure VI. Semi-Constitutive GAPDH Translocation