The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.

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 previou...

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Autores principales: Brian P Carson, Josep Maria Del Bas, Jose Maria Moreno-Navarrete, Jose Manuel Fernandez-Real, Silvia Mora
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:1fa1238fa0df44eabc5d0b7d169d23aa2021-11-18T08:55:41ZThe rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.1932-620310.1371/journal.pone.0074687https://doaj.org/article/1fa1238fa0df44eabc5d0b7d169d23aa2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24040321/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Adiponectin 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.Brian P CarsonJosep Maria Del BasJose Maria Moreno-NavarreteJose Manuel Fernandez-RealSilvia MoraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74687 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Brian P Carson
Josep Maria Del Bas
Jose Maria Moreno-Navarrete
Jose Manuel Fernandez-Real
Silvia Mora
The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
description 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.
format article
author Brian P Carson
Josep Maria Del Bas
Jose Maria Moreno-Navarrete
Jose Manuel Fernandez-Real
Silvia Mora
author_facet Brian P Carson
Josep Maria Del Bas
Jose Maria Moreno-Navarrete
Jose Manuel Fernandez-Real
Silvia Mora
author_sort Brian P Carson
title The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
title_short The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
title_full The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
title_fullStr The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
title_full_unstemmed The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
title_sort rab11 effector protein fip1 regulates adiponectin trafficking and secretion.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/1fa1238fa0df44eabc5d0b7d169d23aa
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