Ferritin is secreted via 2 distinct nonclassical vesicular pathways

Publication Date:
2018-01-19
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Red Cells, Iron, and Erythropoiesis
Published by:
http://www.hematology.org/
_version_ 1836398756727095296
autor Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
beschreibung Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
citation_standardnr 6141643
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-01-19
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/3/342?rss=1
schlagwort Red Cells, Iron, and Erythropoiesis
search_space articles
shingle_author_1 Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
shingle_author_2 Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
shingle_author_3 Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
shingle_author_4 Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
shingle_catch_all_1 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
Red Cells, Iron, and Erythropoiesis
Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
Red Cells, Iron, and Erythropoiesis
Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
Red Cells, Iron, and Erythropoiesis
Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
Red Cells, Iron, and Erythropoiesis
Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis.
Truman-Rosentsvit, M., Berenbaum, D., Spektor, L., Cohen, L. A., Belizowsky-Moshe, S., Lifshitz, L., Ma, J., Li, W., Kesselman, E., Abutbul-Ionita, I., Danino, D., Gutierrez, L., Li, H., Li, K., Lou, H., Regoni, M., Poli, M., Glaser, F., Rouault, T. A., Meyron-Holtz, E. G.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
shingle_title_2 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
shingle_title_3 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
shingle_title_4 Ferritin is secreted via 2 distinct nonclassical vesicular pathways
timestamp 2025-06-30T23:32:07.506Z
titel Ferritin is secreted via 2 distinct nonclassical vesicular pathways
titel_suche Ferritin is secreted via 2 distinct nonclassical vesicular pathways
topic W
WW-YZ
uid ipn_articles_6141643