title: Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes.
abstract: OBJECTIVE
  Upon stimulation of insulin signalling or contraction-induced AMP-activated protein kinase (AMPK) activation, the glucose transporter GLUT4 and the long-chain fatty acid (LCFA) transporter CD36 similarly translocate from intracellular compartments to the plasma membrane of cardiomyocytes to increase uptake of glucose and LCFA, respectively. This similarity in regulation of GLUT4 traffic and CD36 traffic suggests that the same families of trafficking proteins, including vesicle-associated membrane proteins (VAMPs), are involved in both processes. While several VAMPs have been implicated in GLUT4 traffic, nothing is known about the putative function of VAMPs in CD36 traffic. Therefore, we compared the involvement of the myocardially produced VAMP isoforms in insulin- or contraction-induced GLUT4 and CD36 translocation.
  
  
  METHODS
  Five VAMP isoforms were silenced in HL-1 cardiomyocytes. The cells were treated with insulin or the contraction-like AMPK activator oligomycin or were electrically stimulated to contract. Subsequently, GLUT4 and CD36 translocation as well as substrate uptake were measured.
  
  
  RESULTS
  Three VAMPs were demonstrated to be necessary for both GLUT4 and CD36 translocation, either specifically in insulin-treated cells (VAMP2, VAMP5) or in oligomycin/contraction-treated cells (VAMP3). In addition, there are VAMPs specifically involved in either GLUT4 traffic (VAMP7 mediates basal GLUT4 retention) or CD36 traffic (VAMP4 mediates insulin- and oligomycin/contraction-induced CD36 translocation).
  
  
  CONCLUSIONS
  The involvement of distinct VAMP isoforms in both GLUT4 and CD36 translocation indicates that CD36 translocation, just like GLUT4 translocation, is a vesicle-mediated process dependent on soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex formation. The ability of other VAMPs to discriminate between GLUT4 and CD36 translocation allows the notion that myocardial substrate preference can be modulated by these VAMPs.
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. r.schwenk@gen.unimaas.nl
authors.forename: R W
authors.initials: RW
authors.lastname: Schwenk
authors.forename: E
authors.initials: E
authors.lastname: Dirkx
authors.forename: W A
authors.initials: WA
authors.lastname: Coumans
authors.forename: A
authors.initials: A
authors.lastname: Bonen
authors.forename: A
authors.initials: A
authors.lastname: Klip
authors.forename: J F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: J J F P
authors.initials: JJ
authors.lastname: Luiken
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004558:Electric Stimulation; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D050683:R-SNARE Proteins / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D051275:Glucose Transporter Type 4; D007328:Insulin; D009840:Oligomycins; D020033:Protein Isoforms; D050683:R-SNARE Proteins; D055372:AMP-Activated Protein Kinases