Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice

Simonetta Lisi, Roberta Botta, Aldo Pinchera, A. Bernard Collins, Samuel Refetoff, Peter Arvan, Guojun Bu, Lucia Grasso, Vladimir Marshansky, Shaliha Bechoua, Andres Hurtado-Lorenzo, Claudio Marcocci, Dennis Brown, Robert T. McCluskey, Michele Marinò

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11 Scopus citations

Abstract

The molecular chaperone receptor-associated protein (RAP) is required for biosynthesis of megalin, an endocytic receptor for follicular thyroglobulin (Tg), the thyroid hormone precursor. RAP also binds to Tg itself, suggesting that it may affect Tg trafficking in various manners. To elucidate RAP function, we have studied the thyroid phenotype in RAP-knockout (RAP-KO) mice and found a reduction of Tg aggregates into thyroid follicles. Serum Tg levels were significantly increased compared with those of wild-type (WT) mice, suggesting a directional alteration of Tg secretion. In spite of these abnormalities, hormone secretion was maintained as indicated by normal serum thyroxine levels. Because Tg in thyroid extracts from RAP-KO mice contained thyroxine residues as in WT mice, we concluded that in RAP-KO mice, follicular Tg, although reduced, was nevertheless sufficient to provide normal hormone secretion. Serum TSH was increased in RAP-KO mice, and although no thyroid enlargement was observed, some histological features resembling early goiter were present. Megalin was decreased in RAP-KO mice, but this did not affect thyroid function, probably because of the concomitant reduction of follicular Tg. In conclusion, RAP is required for the establishment of Tg reservoirs, but its absence does not affect hormone secretion.

Original languageEnglish (US)
Pages (from-to)C1160-C1167
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number4
DOIs
StatePublished - Apr 1 2006

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Keywords

  • Knockout mice
  • Low-density lipoprotein

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Lisi, S., Botta, R., Pinchera, A., Collins, A. B., Refetoff, S., Arvan, P., Bu, G., Grasso, L., Marshansky, V., Bechoua, S., Hurtado-Lorenzo, A., Marcocci, C., Brown, D., McCluskey, R. T., & Marinò, M. (2006). Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice. American Journal of Physiology - Cell Physiology, 290(4), C1160-C1167. https://doi.org/10.1152/ajpcell.00382.2005