title: The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
abstract: Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNFα. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release.
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, the University of Liverpool, Liverpool, United Kingdom.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Carson
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Del Bas
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Fernandez-Real
authors.forename: Silvia
authors.initials: S
authors.lastname: Mora
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D015992:Body Mass Index; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009765:Obesity / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014168:Transferrin / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D051275:Glucose Transporter Type 4; D008565:Membrane Proteins; D020559:Monomeric GTP-Binding Proteins; D014168:Transferrin; D039221:mRNA Cleavage and Polyadenylation Factors; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C479818:FIP1L1 protein, human; C488966:RAB11FIP1 protein, human; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; C000588698:Fip1l1 protein, mouse
references.citation: J Biol Chem. 1997 Feb 21;272(8):5128-32
references.pmid: 9030579
references.citation: Mol Biol Cell. 2006 Dec;17(12):5298-308
references.pmid: 17035630
references.citation: J Biol Chem. 2000 May 12;275(19):14025-30
references.pmid: 10799475
references.citation: Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1118-28
references.pmid: 17666485
references.citation: J Cell Sci. 2004 Sep 1;117(Pt 19):4365-75
references.pmid: 15304524
references.citation: Science. 1996 Dec 20;274(5295):2100-3
references.pmid: 8953045
references.citation: Traffic. 2007 Feb;8(2):110-23
references.pmid: 17156409
references.citation: Biochim Biophys Acta. 2008 Feb;1782(2):99-108
references.pmid: 18179777
references.citation: Biochem Biophys Res Commun. 2006 Apr 21;342(4):1361-7
references.pmid: 16516854
references.citation: Endocrinology. 2002 Mar;143(3):998-1007
references.pmid: 11861525
references.citation: J Biol Chem. 2001 Oct 19;276(42):39067-75
references.pmid: 11495908
references.citation: Histol Histopathol. 2009 Sep;24(9):1171-80
references.pmid: 19609864
references.citation: Biochem Biophys Res Commun. 2004 Jun 18;319(1):83-94
references.pmid: 15158446
references.citation: J Biol Chem. 2002 Jul 26;277(30):27193-9
references.pmid: 11994279
references.citation: Diabetes. 2002 Oct;51(10):2968-74
references.pmid: 12351435
references.citation: Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E527-33
references.pmid: 12736161
references.citation: Int J Obes (Lond). 2012 Jul;36(7):986-92
references.pmid: 22005720
references.citation: Diabetes. 2002 May;51(5):1319-36
references.pmid: 11978627
references.citation: Biotechniques. 2002 Sep;33(3):654, 656, 658 passim
references.pmid: 12238775
references.citation: J Clin Endocrinol Metab. 2011 Nov;96(11):E1816-25
references.pmid: 21849520
references.citation: Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E326-35
references.pmid: 21540448
references.citation: Biochem Biophys Res Commun. 2006 Jul 14;345(4):1414-24
references.pmid: 16729974
references.citation: Diabetes Care. 2002 Feb;25(2):376-80
references.pmid: 11815513
references.citation: Mol Biol Cell. 2004 May;15(5):2456-69
references.pmid: 15004234
references.citation: Diabetologia. 2011 Jun;54(6):1480-90
references.pmid: 21400042
references.citation: J Cell Sci. 2010 Jan 15;123(Pt 2):181-91
references.pmid: 20026645
references.citation: Traffic. 2004 Oct;5(10):785-97
references.pmid: 15355514
references.citation: J Intern Med. 2005 Feb;257(2):167-75
references.pmid: 15656875
references.citation: J Biol Chem. 2003 Aug 22;278(34):31486-94
references.pmid: 12796484
references.citation: J Cell Sci. 2007 Dec 1;120(Pt 23):4197-208
references.pmid: 18003705
references.citation: J Biol Chem. 2006 Mar 17;281(11):7253-9
references.pmid: 16407204
references.citation: Biol Cell. 2009 Oct 12;102(1):51-62
references.pmid: 19702578
references.citation: Biochem Biophys Res Commun. 2003 Nov 14;311(2):372-9
references.pmid: 14592424
references.citation: J Biol Chem. 1995 Nov 10;270(45):26746-9
references.pmid: 7592907
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1833-42
references.pmid: 16608874
references.citation: Mol Biol Cell. 2004 Aug;15(8):3530-41
references.pmid: 15181150
references.citation: Nat Med. 2001 Aug;7(8):947-53
references.pmid: 11479628
references.citation: Traffic. 2000 Feb;1(2):141-51
references.pmid: 11208094
references.citation: J Clin Invest. 2001 Dec;108(12):1875-81
references.pmid: 11748271
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2005-10
references.pmid: 11172066
references.citation: Nat Med. 2001 Aug;7(8):941-6
references.pmid: 11479627
references.citation: Mol Biol Cell. 2010 Sep 1;21(17):3041-53
references.pmid: 20610657
references.citation: Biochem Biophys Res Commun. 1996 Apr 16;221(2):286-9
references.pmid: 8619847
references.citation: J Biol Chem. 1997 Jan 10;272(2):971-6
references.pmid: 8995390
references.citation: Biochem Pharmacol. 2010 May 1;79(9):1300-9
references.pmid: 20026082
references.citation: J Biol Chem. 1996 May 3;271(18):10697-703
references.pmid: 8631877
references.citation: Biochem Soc Trans. 2009 Oct;37(Pt 5):1032-6
references.pmid: 19754446
references.citation: Biochem Biophys Res Commun. 2010 Apr 2;394(2):387-92
references.pmid: 20214888