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© The Rockefeller University Press, 0021-9525/1997//1243 $5.00
The Journal of Cell Biology, Volume 137, Number 6, , 1997 1243-1254

Article

Glucose Transporter (GLUT-4) Is Targeted to Secretory Granules in Rat Atrial Cardiomyocytes



Jan W. Slot*,{ddagger}, Gabriella Garruti*,¶, Sally Martin{ddagger}, Viola Oorschot*, George Posthuma*, Edward W. Kraegen§, Ross Laybutt§, Gaétan Thibault||, and David E. James{ddagger}

* Department of Cell Biology, Medical School, Utrecht University, 3584 CX Utrecht, The Netherlands; {ddagger} 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

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.

1. Abbreviations used in this paper: ANF, atrial natriuretic factor; LM, light microscopy; MPR, mannose 6-phosphate receptor; 2DG, 2-deoxyglucose; TGR, trans-Golgi reticulum; T-V, tubulo-vesicular.

Please address all correspondence to Jan W. Slot, Department of Cell Biology, Medical School, Utrecht University, AZU Room H02.314, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Tel.: (31) 30-2507654. Fax: (31) 30-2541797.


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