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Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice
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Zeitschriftentitel: | American Journal of Physiology-Cell Physiology |
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Personen und Körperschaften: | , , , , , , , , , , , , , , |
In: | American Journal of Physiology-Cell Physiology, 290, 2006, 4, S. C1160-C1167 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Physiological Society
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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 |
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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 |
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 |
doi_str_mv |
10.1152/ajpcell.00382.2005 |
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American Physiological Society |
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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 |
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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 |