Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects

Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alfredo Ulloa-Aguirre, Teresa Zariñán, Eduardo Jardón-Valadez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	G protein-coupled receptors GPCR protein misfolding mutations in GPCRs loss-of-function diseases gonadotropin-releasing hormone receptor Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5cdcd84ca904425f90ea37a28ca25812
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5cdcd84ca904425f90ea37a28ca25812
record_format	dspace
spelling	oai:doaj.org-article:5cdcd84ca904425f90ea37a28ca258122021-11-25T17:55:27ZMisfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects10.3390/ijms2222123291422-00671661-6596https://doaj.org/article/5cdcd84ca904425f90ea37a28ca258122021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12329https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes insipidus, thyroid disorders, familial hypocalciuric hypercalcemia, obesity, familial glucocorticoid deficiency [melanocortin-2 receptor, MC2R (also known as adrenocorticotropin receptor, ACTHR), and reproductive disorders. In these mutant receptors, misfolding leads to endoplasmic reticulum retention, increased intracellular degradation, and deficient trafficking of the abnormal receptor to the cell surface plasma membrane, causing inability of the receptor to interact with agonists and trigger intracellular signaling. In this review, we discuss the mechanisms whereby mutations in GPCRs involved in endocrine function in humans lead to misfolding, decreased plasma membrane expression of the receptor protein, and loss-of-function diseases, and also describe several experimental approaches employed to rescue trafficking and function of the misfolded receptors. Special attention is given to misfolded GPCRs that regulate reproductive function, given the key role played by these particular membrane receptors in sexual development and fertility, and recent reports on promising therapeutic interventions targeting trafficking of these defective proteins to rescue completely or partially their normal function.Alfredo Ulloa-AguirreTeresa ZariñánEduardo Jardón-ValadezMDPI AGarticleG protein-coupled receptorsGPCRprotein misfoldingmutations in GPCRsloss-of-function diseasesgonadotropin-releasing hormone receptorBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12329, p 12329 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	G protein-coupled receptors GPCR protein misfolding mutations in GPCRs loss-of-function diseases gonadotropin-releasing hormone receptor Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	G protein-coupled receptors GPCR protein misfolding mutations in GPCRs loss-of-function diseases gonadotropin-releasing hormone receptor Biology (General) QH301-705.5 Chemistry QD1-999 Alfredo Ulloa-Aguirre Teresa Zariñán Eduardo Jardón-Valadez Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
description	Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes insipidus, thyroid disorders, familial hypocalciuric hypercalcemia, obesity, familial glucocorticoid deficiency [melanocortin-2 receptor, MC2R (also known as adrenocorticotropin receptor, ACTHR), and reproductive disorders. In these mutant receptors, misfolding leads to endoplasmic reticulum retention, increased intracellular degradation, and deficient trafficking of the abnormal receptor to the cell surface plasma membrane, causing inability of the receptor to interact with agonists and trigger intracellular signaling. In this review, we discuss the mechanisms whereby mutations in GPCRs involved in endocrine function in humans lead to misfolding, decreased plasma membrane expression of the receptor protein, and loss-of-function diseases, and also describe several experimental approaches employed to rescue trafficking and function of the misfolded receptors. Special attention is given to misfolded GPCRs that regulate reproductive function, given the key role played by these particular membrane receptors in sexual development and fertility, and recent reports on promising therapeutic interventions targeting trafficking of these defective proteins to rescue completely or partially their normal function.
format	article
author	Alfredo Ulloa-Aguirre Teresa Zariñán Eduardo Jardón-Valadez
author_facet	Alfredo Ulloa-Aguirre Teresa Zariñán Eduardo Jardón-Valadez
author_sort	Alfredo Ulloa-Aguirre
title	Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
title_short	Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
title_full	Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
title_fullStr	Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
title_full_unstemmed	Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects
title_sort	misfolded g protein-coupled receptors and endocrine disease. molecular mechanisms and therapeutic prospects
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5cdcd84ca904425f90ea37a28ca25812
work_keys_str_mv	AT alfredoulloaaguirre misfoldedgproteincoupledreceptorsandendocrinediseasemolecularmechanismsandtherapeuticprospects AT teresazarinan misfoldedgproteincoupledreceptorsandendocrinediseasemolecularmechanismsandtherapeuticprospects AT eduardojardonvaladez misfoldedgproteincoupledreceptorsandendocrinediseasemolecularmechanismsandtherapeuticprospects
_version_	1718411804120449024

Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects

Ejemplares similares