title: Glucose transporter (GLUT-4) is targeted to secretory granules in rat atrial cardiomyocytes.
abstract: The insulin-responsive glucose transporter GLUT-4 is found in muscle and fat cells in the trans-Golgi reticulum (TGR) and in an intracellular tubulovesicular compartment, from where it undergoes insulin-dependent 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.
authors.affiliation: Department of Cell Biology, Medical School, Utrecht University, 3584 CX Utrecht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Slot
authors.forename: G
authors.initials: G
authors.lastname: Garruti
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: V
authors.initials: V
authors.lastname: Oorschot
authors.forename: G
authors.initials: G
authors.lastname: Posthuma
authors.forename: E W
authors.initials: EW
authors.lastname: Kraegen
authors.forename: R
authors.initials: R
authors.lastname: Laybutt
authors.forename: G
authors.initials: G
authors.lastname: Thibault
authors.forename: D E
authors.initials: DE
authors.lastname: James
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011500:Protein Synthesis Inhibitors; C495694:Slc2a4 protein, rat; D003513:Cycloheximide