Neutrophil Adhesion and Migration: Another Role of the Glucose-6-Phosphate Transporter

Abstract

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in a glucose-6-phosphate transporter (G6PT) that belongs to the solute-carrier-37 family of endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate exchangers [1,2]. The primary in vivo function of the ubiquitously expressed G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α) or the ubiquitously expressed G6Pase-ß to hydrolyze G6P to glucose and phosphate [3,4]. The G6PT/G6Pase-α complex maintains interprandial glucose homeostasis and the G6PT/G6Pase-ß complex maintains neutrophil energy homeostasis and functionality. Therefore, GSD-Ib is an autosomal recessive metabolic and immune disorder characterized by impaired glucose homeostasis, neutropenia and neutrophil dysfunction [3,4]. Recently, we showed that G6PTdeficient neutrophils from GSD-Ib patients receiving granulocytecolony stimulating factor (G-CSF) therapy exhibited impaired energy homeostasis and function [5], suggesting that G6PT-regulated G6P metabolism is important for neutrophil function. However, G-CSF failed to correct impaired neutrophil energy homeostasis in GSD-Ib [5].