Loss of function mutations of thyrotropin receptor (TSHR) are one of the main causes of congenital hypothyroidism (CH). As for many disease-associated G-protein coupled receptors (GPCRs), these mutations often affect the correct trafficking and maturation of the receptor, thus impairing the expression on the cell surface. Several retained GPCR mutants are able to effectively bind their ligands and to transduce signals when they are forced to the cell surface by degradation inhibition or by treatment with chaperones. Despite the large number of well-characterized retained TSHR mutants, no attempts have been made for rescue. Furthermore, little is known about TSHR degradation pathways. We hypothesize that, similarly to other GPCRs, TSHR retained mutants may be at least partially functional if their maturation and membrane expression is facilitated by chaperones or degradation inhibitors.
Thyrotropin receptor p.N432D retained variant is degraded through an alternative lysosomal/autophagosomal pathway and can be functionally rescued by chemical chaperones / E.S. Grassi, A. Labadi, V. Vezzoli, V. Ghiandai, M. Bonomi, L. Persani. - In: THYROID. - ISSN 1050-7256. - 31:7(2021 Jul), pp. 1030-1040. [10.1089/thy.2020.0415]
Titolo: | Thyrotropin receptor p.N432D retained variant is degraded through an alternative lysosomal/autophagosomal pathway and can be functionally rescued by chemical chaperones | |
Autori: | GRASSI, ELISA STELLARIA (Co-primo) PERSANI, LUCA (Ultimo) (Corresponding) | |
Parole Chiave: | thyrotropin receptor; congenital hypothyroidism; G protein coupled receptor; chaperone; autophagosome; functional rehabilitation | |
Settore Scientifico Disciplinare: | Settore MED/13 - Endocrinologia | |
Data di pubblicazione: | lug-2021 | |
Rivista: | ||
Tipologia: | Article (author) | |
Data ahead of print / Data di stampa: | 22-feb-2021 | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1089/thy.2020.0415 | |
Appare nelle tipologie: | 01 - Articolo su periodico |
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