Role of Microtubules in Lipoprotein Secretion by the Liver

Abstract

TRIGLYCERIDE-rich lipoprotein particles, in particular the very low density lipoproteins (VLDL), are important secretory products of the liver¹. In the study of the formation and release of these particles, progress has been made by the demonstration that VLDL can be visualized by electron microscopy as electron-opaque particles, diameter 300–1000 Å (ref. 2). This makes it possible to follow the time sequence of their intracellular migration from their site of formation to that of their release into the extracellular space. Although there is evidence that final discharge of these particles into the space of Disse occurs through fusion of the membrane of the vacuoles which contain lipoproteins, with the plasma membrane², the mechanisms governing the intracellular translocation of the VLDL particles are still unknown. Circumstantial evidence has led to the suggestion that microtubules and microfilaments are part of a contractile system of the cell which plays an important role in the secretory processes of several different cell types^3–9. To investigate the possibility that microtubules are also involved in the secretion of lipoprotein particles by the liver, we made use of the mitotic-spindle inhibitors, vincristine and colchicine, agents which interact with these structures and interfere, probably selectively, with their function^10–13. Using this approach, we report here a marked decrease in triglyceride-rich lipoprotein particle release by livers perfused in the presence of mitotic-spindle inhibitors.