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SORCS1 and SORCS3 control energy balance and orexigenic peptide production

SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 a...

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Autores principales: Subkhangulova, Aygul, Malik, Anna R, Hermey, Guido, Popp, Oliver, Dittmar, Gunnar, Rathjen, Thomas, Poy, Matthew N, Stumpf, Alexander, Beed, Prateep Sanker, Schmitz, Dietmar, Breiderhoff, Tilman, Willnow, Thomas E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891432/
https://www.ncbi.nlm.nih.gov/pubmed/29440124
http://dx.doi.org/10.15252/embr.201744810
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author Subkhangulova, Aygul
Malik, Anna R
Hermey, Guido
Popp, Oliver
Dittmar, Gunnar
Rathjen, Thomas
Poy, Matthew N
Stumpf, Alexander
Beed, Prateep Sanker
Schmitz, Dietmar
Breiderhoff, Tilman
Willnow, Thomas E
author_facet Subkhangulova, Aygul
Malik, Anna R
Hermey, Guido
Popp, Oliver
Dittmar, Gunnar
Rathjen, Thomas
Poy, Matthew N
Stumpf, Alexander
Beed, Prateep Sanker
Schmitz, Dietmar
Breiderhoff, Tilman
Willnow, Thomas E
author_sort Subkhangulova, Aygul
collection PubMed
description SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin‐related kinase B to attenuate signaling by brain‐derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti‐related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight. Our findings highlight a novel concept in regulation of the melanocortin system and the role played by trafficking receptors SORCS1 and SORCS3 in this process.
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spelling pubmed-58914322018-04-13 SORCS1 and SORCS3 control energy balance and orexigenic peptide production Subkhangulova, Aygul Malik, Anna R Hermey, Guido Popp, Oliver Dittmar, Gunnar Rathjen, Thomas Poy, Matthew N Stumpf, Alexander Beed, Prateep Sanker Schmitz, Dietmar Breiderhoff, Tilman Willnow, Thomas E EMBO Rep Articles SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin‐related kinase B to attenuate signaling by brain‐derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti‐related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight. Our findings highlight a novel concept in regulation of the melanocortin system and the role played by trafficking receptors SORCS1 and SORCS3 in this process. John Wiley and Sons Inc. 2018-02-12 2018-04 /pmc/articles/PMC5891432/ /pubmed/29440124 http://dx.doi.org/10.15252/embr.201744810 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Subkhangulova, Aygul
Malik, Anna R
Hermey, Guido
Popp, Oliver
Dittmar, Gunnar
Rathjen, Thomas
Poy, Matthew N
Stumpf, Alexander
Beed, Prateep Sanker
Schmitz, Dietmar
Breiderhoff, Tilman
Willnow, Thomas E
SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title_full SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title_fullStr SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title_full_unstemmed SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title_short SORCS1 and SORCS3 control energy balance and orexigenic peptide production
title_sort sorcs1 and sorcs3 control energy balance and orexigenic peptide production
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891432/
https://www.ncbi.nlm.nih.gov/pubmed/29440124
http://dx.doi.org/10.15252/embr.201744810
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