Transaldolase is part of a supramolecular complex containing glucose-6-phosphate dehydrogenase in human neutrophils that undergoes retrograde trafficking during pregnancy.
Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PDase) and 6-phosphogluconate dehydrogenase form a supramolecular complex in human neutrophils that undergoes retrograde trafficking in cells from pregnant women, but anterograde trafficking in cells from nonpregnant individuals. Using fluorescence resonance energy transfer techniques, we now demonstrate that transaldolase (TALase), a key regulatory enzyme in the nonoxidative branch of the hexose monophosphate shunt, is in close physical proximity with G6PDase, but not with lactate dehydrogenase, thus suggesting the formation of a TALase-G6PDase complex. Moreover, immunofluorescence microscopy demonstrated that TALase undergoes anterograde trafficking in neutrophils from nonpregnant individuals, whereas retrograde trafficking is found during pregnancy. However, pregnancy did not affect lactate dehydrogenase distribution. Colchicine treatment blocked the retrograde distribution of TALase, suggesting that microtubules are involved in TALase trafficking. We suggest that TALase is part of a supramolecular hexose monophosphate shunt complex, which likely increases the efficiency of the shunt via substrate channeling. We further suggest that TALase's retrograde motion contributes to uncoupling the shunt from its source of glucose-6-phosphate at the plasma membrane, thereby blunting nicotinamide adenine dinucleotide phosphate (reduced form) production and downstream oxidant production by neutrophils.
Huang
Ji-Biao
JB
Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Espinoza
Jimmy
J
Romero
Roberto
R
Petty
Howard R
HR
D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D010427:Pentose Phosphate Pathway / Q000276:immunology; D011247:Pregnancy / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000276:immunology; D014153:Transaldolase / Q000378:metabolism*
D009097:Multienzyme Complexes; D005954:Glucosephosphate Dehydrogenase; D014153:Transaldolase