Differential involvement of caveolin-1 in brown adipocyte signaling: impaired beta3-adrenergic, but unaffected LPA, PDGF and EGF receptor signaling.
Caveolae and caveolin have been implicated as being involved in the signal transduction of many receptors, including the EGF, PDGF, LPA and beta3-adrenergic receptors. To investigate the role of caveolin-1 (Cav1) in these signaling pathways in brown adipose tissue, primary brown adipocyte cultures from Cav1-ablated mice and wild-type mice were investigated. In pre-adipocytes, Cav1-ablation affected neither the G-protein coupled LPA receptor signaling to Erk1/2, nor the receptor tyrosine kinases PDGF- or EGF-receptor signaling to Erk1/2. Mature primary Cav1-/- brown adipocytes accumulated lipids and expressed aP2 to the same extent as did wild-type cells. However, the cAMP levels induced by the beta3-adrenergic receptor agonist CL316,243 were lower in the Cav1-/- cultures, with an unchanged EC50 for CL316,243. Also the response to the direct adenylyl cyclase agonist forskolin was reduced. Thus, in brown adipocytes, Cav1 is apparently required for an intact response to adenylyl cyclase-linked agonists/activators, whereas other signaling pathways examined function without Cav1.
Mattsson
Charlotte L
CL
Department of Physiology, The Wenner-Gren Institute, The Arrhenius laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Andersson
Emma R
ER
Nedergaard
Jan
J
D052437:Adipocytes, Brown / Q000166:cytology / Q000502:physiology*; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004149:Dioxoles / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D051242:Caveolin 1; D004149:Dioxoles; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D022702:Receptors, Adrenergic, beta-3; D049368:Receptors, Lysophosphatidic Acid; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D005576:Colforsin; D000242:Cyclic AMP; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3