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* Department of Cell Biology, Medical School, Utrecht University, 3584 CX Utrecht, The Netherlands; The insulin-responsive glucose transporter
GLUT-4 is found in muscle and fat cells in the transGolgi reticulum (TGR) and in an intracellular tubulovesicular compartment, from where it undergoes insulindependent movement to the cell surface. To examine
the relationship between these GLUT-4-containing
compartments and the regulated secretory pathway we
have localized GLUT-4 in atrial cardiomyocytes. This
cell type secretes an antihypertensive hormone, referred to as the atrial natriuretic factor (ANF), in response to elevated blood pressure. We show that
GLUT-4 is targeted in the atrial cell to the TGR and a
tubulo-vesicular compartment, which is morphologically and functionally indistinguishable from the intracellular GLUT-4 compartment found in other types of
myocytes and in fat cells, and in addition to the ANF
secretory granules. Forming ANF granules are present
throughout all Golgi cisternae but only become GLUT4 positive in the TGR. The inability of cyclohexamide treatment to effect the TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory granules at the TGR via the recycling pathway and not via
the biosynthetic pathway. These data suggest that a
large proportion of GLUT-4 must recycle via the TGR
in insulin-sensitive cells. It will be important to determine if this is the pathway by which the insulin-regulatable tubulo-vesicular compartment is formed.
Centre for Molecular
and Cellular Biology, University of Queensland, St. Lucia, QLD, 4072, Australia; § Garvan Institute of Medical Research, St.
Vincents Hospital, Darlinghurst, NSW, 2010, Australia;
Cell Biology of Hypertension, Clinical Research Institute of Montreal,
Montreal, Quebec, H2W 1R7, Canada; and ¶ Endocrinology and Metabolic Diseases, Institute of Medicine, University of Bari,
70124 Bari, Italy
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