author_facet Lisi, Simonetta
Botta, Roberta
Pinchera, Aldo
Collins, A. Bernard
Refetoff, Samuel
Arvan, Peter
Bu, Guojun
Grasso, Lucia
Marshansky, Vladimir
Bechoua, Shaliha
Hurtado-Lorenzo, Andres
Marcocci, Claudio
Brown, Dennis
McCluskey, Robert T.
Marinò, Michele
Lisi, Simonetta
Botta, Roberta
Pinchera, Aldo
Collins, A. Bernard
Refetoff, Samuel
Arvan, Peter
Bu, Guojun
Grasso, Lucia
Marshansky, Vladimir
Bechoua, Shaliha
Hurtado-Lorenzo, Andres
Marcocci, Claudio
Brown, Dennis
McCluskey, Robert T.
Marinò, Michele
author Lisi, Simonetta
Botta, Roberta
Pinchera, Aldo
Collins, A. Bernard
Refetoff, Samuel
Arvan, Peter
Bu, Guojun
Grasso, Lucia
Marshansky, Vladimir
Bechoua, Shaliha
Hurtado-Lorenzo, Andres
Marcocci, Claudio
Brown, Dennis
McCluskey, Robert T.
Marinò, Michele
spellingShingle Lisi, Simonetta
Botta, Roberta
Pinchera, Aldo
Collins, A. Bernard
Refetoff, Samuel
Arvan, Peter
Bu, Guojun
Grasso, Lucia
Marshansky, Vladimir
Bechoua, Shaliha
Hurtado-Lorenzo, Andres
Marcocci, Claudio
Brown, Dennis
McCluskey, Robert T.
Marinò, Michele
American Journal of Physiology-Cell Physiology
Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
Cell Biology
Physiology
author_sort lisi, simonetta
spelling Lisi, Simonetta Botta, Roberta Pinchera, Aldo Collins, A. Bernard Refetoff, Samuel Arvan, Peter Bu, Guojun Grasso, Lucia Marshansky, Vladimir Bechoua, Shaliha Hurtado-Lorenzo, Andres Marcocci, Claudio Brown, Dennis McCluskey, Robert T. Marinò, Michele 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00382.2005 <jats:p>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.</jats:p> Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice American Journal of Physiology-Cell Physiology
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series American Journal of Physiology-Cell Physiology
source_id 49
title Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_unstemmed Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_full Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_fullStr Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_full_unstemmed Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_short Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_sort defective thyroglobulin storage in ldl receptor-associated protein-deficient mice
topic Cell Biology
Physiology
url http://dx.doi.org/10.1152/ajpcell.00382.2005
publishDate 2006
physical C1160-C1167
description <jats:p>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.</jats:p>
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author Lisi, Simonetta, Botta, Roberta, Pinchera, Aldo, Collins, A. Bernard, Refetoff, Samuel, Arvan, Peter, Bu, Guojun, Grasso, Lucia, Marshansky, Vladimir, Bechoua, Shaliha, Hurtado-Lorenzo, Andres, Marcocci, Claudio, Brown, Dennis, McCluskey, Robert T., Marinò, Michele
author_facet Lisi, Simonetta, Botta, Roberta, Pinchera, Aldo, Collins, A. Bernard, Refetoff, Samuel, Arvan, Peter, Bu, Guojun, Grasso, Lucia, Marshansky, Vladimir, Bechoua, Shaliha, Hurtado-Lorenzo, Andres, Marcocci, Claudio, Brown, Dennis, McCluskey, Robert T., Marinò, Michele, Lisi, Simonetta, Botta, Roberta, Pinchera, Aldo, Collins, A. Bernard, Refetoff, Samuel, Arvan, Peter, Bu, Guojun, Grasso, Lucia, Marshansky, Vladimir, Bechoua, Shaliha, Hurtado-Lorenzo, Andres, Marcocci, Claudio, Brown, Dennis, McCluskey, Robert T., Marinò, Michele
author_sort lisi, simonetta
container_issue 4
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container_title American Journal of Physiology-Cell Physiology
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description <jats:p>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.</jats:p>
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spelling Lisi, Simonetta Botta, Roberta Pinchera, Aldo Collins, A. Bernard Refetoff, Samuel Arvan, Peter Bu, Guojun Grasso, Lucia Marshansky, Vladimir Bechoua, Shaliha Hurtado-Lorenzo, Andres Marcocci, Claudio Brown, Dennis McCluskey, Robert T. Marinò, Michele 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00382.2005 <jats:p>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.</jats:p> Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice American Journal of Physiology-Cell Physiology
spellingShingle Lisi, Simonetta, Botta, Roberta, Pinchera, Aldo, Collins, A. Bernard, Refetoff, Samuel, Arvan, Peter, Bu, Guojun, Grasso, Lucia, Marshansky, Vladimir, Bechoua, Shaliha, Hurtado-Lorenzo, Andres, Marcocci, Claudio, Brown, Dennis, McCluskey, Robert T., Marinò, Michele, American Journal of Physiology-Cell Physiology, Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice, Cell Biology, Physiology
title Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_full Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_fullStr Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_full_unstemmed Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_short Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
title_sort defective thyroglobulin storage in ldl receptor-associated protein-deficient mice
title_unstemmed Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
topic Cell Biology, Physiology
url http://dx.doi.org/10.1152/ajpcell.00382.2005