title: ACRP30 is secreted from 3T3-L1 adipocytes via a Rab11-dependent pathway.
abstract: Adipocytes are now known to secrete a range of adipokines that exhibit distinct biological functions. Here, we sought to understand the secretory pathways utilised by ACRP30 to the surface of adipocytes. We find that ACRP30 overlaps with adipsin in intracellular compartments distinct from Glut4, but nonetheless exhibits insulin-stimulated secretion from cells. Both adipsin and ACRP30 overlap with transferrin receptor-positive membranes, implying that the pathway of secretion involves the transferrin receptor-positive endosomal system. Consistent with this, we show that ablation of endosomes significantly inhibited the secretion of ACRP30, as did treatment of cells with Brefeldin A. In order to further probe the role of recycling endosomes on the secretion of ACRP30, we over-expressed a mutant form of Rab11, Rab11-S25N, in 3T3-L1 adipocytes and found that expression of this mutant significantly reduced basal and insulin-stimulated secretion. We also demonstrate that Arf6 also plays a role in the secretion of ACRP30. Collectively, these data implicate both Arf6 and Rab11 as crucial mediators of constitutive and insulin-stimulated secretion of ACRP30 and further suggest that recycling endosomes may play a central role in this process.
authors.affiliation: Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, Scotland, UK.
authors.forename: Mairi
authors.initials: M
authors.lastname: Clarke
authors.forename: Marie-Ann
authors.initials: MA
authors.lastname: Ewart
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Santy
authors.forename: Rytis
authors.initials: R
authors.lastname: Prekeris
authors.forename: Gwyn W
authors.initials: GW
authors.lastname: Gould
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D011992:Endosomes / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D052242:Adiponectin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C499919:Adipoq protein, mouse