Sortilin is a putative postendocytic receptor of thyroglobulin

Roberta Botta, Simonetta Lisi, Aldo Pinchera, Franco Giorgi, Claudio Marcocci, Anna Rita Taddei, Anna Maria Fausto, Nunzia Bernardini, Chiara Ippolito, Letizia Mattii, Luca Persani, Tiziana De Filippis, Davide Calebiro, Peder Madsen, Claus Munck Petersen, Michele Marinò

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Abstract

The Vps10p family member sortilin is involved in various cell processes, including protein trafficking. Here we found that sortilin is expressed in thyroid epithelial cells (thyrocytes) in a TSH-dependent manner, that the hormone precursor thyroglobulin (Tg) is a high-affinity sortilin ligand, and that binding to sortilin occurs after Tg endocytosis, resulting inTg recycling. Sortilin was found to be expressed intracellularly in thyrocytes, as observed in mouse, human, and rat thyroid as well as in FRTL-5 cells. Sortilin expression was demonstrated to be TSH dependent, both in FRTL-5 cells and in mice treated with methimazole and perchlorate. Plasmon resonance binding assays showed that Tg binds to sortilin in a concentration-dependent manner and with high affinity, with Kd values that paralleled the hormone content of Tg. In addition, we found that Tg and sortilin interact in vivo and in cultured cells, as observed by immunoprecipitation, in mouse thyroid extracts and in COS-7 cells transiently cotransfected with sortilin and Tg. After incubation of FRTL-5 cells with exogenous, labeled Tg, sortilin and Tg interacted intracellularly, presumably within the endocytic pathway, as observed by immunofluorescence and immunoelectron microscopy, the latter technique showing some degree of Tg recycling. This was confirmed in FRTL-5 cells in which Tg recycling was reduced by silencing of the sortilin gene and in CHO cells transfected with sortilin in which recycling was increased. Our findings provide a novel pathway of Tg trafficking and a novel function of sortilin in the thyroid gland, the functional impact of which remains to be established. (Endocrinology 150: 509-518, 2009)

Original languageEnglish
Pages (from-to)509
Number of pages1
JournalEndocrinology
Volume150
Issue number1
DOIs
Publication statusPublished - Jan 2009

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Thyroglobulin
Recycling
Thyroid Gland
thyroglobulin receptor
sortilin
Hormones
Methimazole
Immunoelectron Microscopy
CHO Cells
Endocrinology
COS Cells
Gene Silencing
Protein Transport
Endocytosis
Fluorescence Microscopy
Immunoprecipitation
Cultured Cells
Ligands

ASJC Scopus subject areas

  • Endocrinology

Cite this

Botta, R., Lisi, S., Pinchera, A., Giorgi, F., Marcocci, C., Taddei, A. R., ... Marinò, M. (2009). Sortilin is a putative postendocytic receptor of thyroglobulin. Endocrinology, 150(1), 509. https://doi.org/10.1210/en.2008-0953

Sortilin is a putative postendocytic receptor of thyroglobulin. / Botta, Roberta; Lisi, Simonetta; Pinchera, Aldo; Giorgi, Franco; Marcocci, Claudio; Taddei, Anna Rita; Fausto, Anna Maria; Bernardini, Nunzia; Ippolito, Chiara; Mattii, Letizia; Persani, Luca; De Filippis, Tiziana; Calebiro, Davide; Madsen, Peder; Petersen, Claus Munck; Marinò, Michele.

In: Endocrinology, Vol. 150, No. 1, 01.2009, p. 509.

Research output: Contribution to journalArticle

Botta, R, Lisi, S, Pinchera, A, Giorgi, F, Marcocci, C, Taddei, AR, Fausto, AM, Bernardini, N, Ippolito, C, Mattii, L, Persani, L, De Filippis, T, Calebiro, D, Madsen, P, Petersen, CM & Marinò, M 2009, 'Sortilin is a putative postendocytic receptor of thyroglobulin', Endocrinology, vol. 150, no. 1, pp. 509. https://doi.org/10.1210/en.2008-0953
Botta R, Lisi S, Pinchera A, Giorgi F, Marcocci C, Taddei AR et al. Sortilin is a putative postendocytic receptor of thyroglobulin. Endocrinology. 2009 Jan;150(1):509. https://doi.org/10.1210/en.2008-0953
Botta, Roberta ; Lisi, Simonetta ; Pinchera, Aldo ; Giorgi, Franco ; Marcocci, Claudio ; Taddei, Anna Rita ; Fausto, Anna Maria ; Bernardini, Nunzia ; Ippolito, Chiara ; Mattii, Letizia ; Persani, Luca ; De Filippis, Tiziana ; Calebiro, Davide ; Madsen, Peder ; Petersen, Claus Munck ; Marinò, Michele. / Sortilin is a putative postendocytic receptor of thyroglobulin. In: Endocrinology. 2009 ; Vol. 150, No. 1. pp. 509.
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abstract = "The Vps10p family member sortilin is involved in various cell processes, including protein trafficking. Here we found that sortilin is expressed in thyroid epithelial cells (thyrocytes) in a TSH-dependent manner, that the hormone precursor thyroglobulin (Tg) is a high-affinity sortilin ligand, and that binding to sortilin occurs after Tg endocytosis, resulting inTg recycling. Sortilin was found to be expressed intracellularly in thyrocytes, as observed in mouse, human, and rat thyroid as well as in FRTL-5 cells. Sortilin expression was demonstrated to be TSH dependent, both in FRTL-5 cells and in mice treated with methimazole and perchlorate. Plasmon resonance binding assays showed that Tg binds to sortilin in a concentration-dependent manner and with high affinity, with Kd values that paralleled the hormone content of Tg. In addition, we found that Tg and sortilin interact in vivo and in cultured cells, as observed by immunoprecipitation, in mouse thyroid extracts and in COS-7 cells transiently cotransfected with sortilin and Tg. After incubation of FRTL-5 cells with exogenous, labeled Tg, sortilin and Tg interacted intracellularly, presumably within the endocytic pathway, as observed by immunofluorescence and immunoelectron microscopy, the latter technique showing some degree of Tg recycling. This was confirmed in FRTL-5 cells in which Tg recycling was reduced by silencing of the sortilin gene and in CHO cells transfected with sortilin in which recycling was increased. Our findings provide a novel pathway of Tg trafficking and a novel function of sortilin in the thyroid gland, the functional impact of which remains to be established. (Endocrinology 150: 509-518, 2009)",
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