Cellular fate and functions of glucosylceramide

Abstract

The organization of the synthesis of sphingomyelin and the simple glycosphingolipids in the Golgi appears to be highly important not only for creating sphingolipid/cholesterol rafts in the late Golgi but also for regulating numerous protein glycosylation, processing and sorting steps in the Golgi lumen via an intricate mechanism of pH regulation. The universal character of this regulatory system predicts that it represents one basic link between very different physiological parameters, sphingolipid homeostasis and pH regulation. This discovery may have an impact on developing cures for diseases of sphingolipid metabolism, like Gaucher and Farber disease, where the cellular accumulations of glucosylceramide and ceramide may actually induce pathogenesis via an effect on pH. On the other hand, the discovery of the role of pH in pigmentation may contribute to a better understanding of various forms of oculocutaneous albinism for which the disease mechanism had remained unclear.