Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation
Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) an...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2014
|
| Online Access: | http://hdl.handle.net/1721.1/86052 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1826211129471270912 |
|---|---|
| author | Chen, Caiyong Garcia-Santos, Daniel Ishikawa, Yuichi Seguin, Alexandra Li, Liangtao Fegan, Katherine H. Hildick-Smith, Gordon J. Shah, Dhvanit I. Cooney, Jeffrey D. Chen, Wen King, Matthew J. Yien, Yvette Y. Schultz, Iman J. Anderson, Heidi Dalton, Arthur J. Freedman, Matthew L. Kingsley, Paul D. Palis, James Hattangadi, Shilpa M. Ward, Diane M. Kaplan, Jerry Maeda, Takahiro Ponka, Prem Paw, Barry H. Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chen, Caiyong Garcia-Santos, Daniel Ishikawa, Yuichi Seguin, Alexandra Li, Liangtao Fegan, Katherine H. Hildick-Smith, Gordon J. Shah, Dhvanit I. Cooney, Jeffrey D. Chen, Wen King, Matthew J. Yien, Yvette Y. Schultz, Iman J. Anderson, Heidi Dalton, Arthur J. Freedman, Matthew L. Kingsley, Paul D. Palis, James Hattangadi, Shilpa M. Ward, Diane M. Kaplan, Jerry Maeda, Takahiro Ponka, Prem Paw, Barry H. Lodish, Harvey F |
| author_sort | Chen, Caiyong |
| collection | MIT |
| description | Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism. |
| first_indexed | 2024-09-23T15:01:03Z |
| format | Article |
| id | mit-1721.1/86052 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:01:03Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/860522022-09-29T12:04:06Z Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation Chen, Caiyong Garcia-Santos, Daniel Ishikawa, Yuichi Seguin, Alexandra Li, Liangtao Fegan, Katherine H. Hildick-Smith, Gordon J. Shah, Dhvanit I. Cooney, Jeffrey D. Chen, Wen King, Matthew J. Yien, Yvette Y. Schultz, Iman J. Anderson, Heidi Dalton, Arthur J. Freedman, Matthew L. Kingsley, Paul D. Palis, James Hattangadi, Shilpa M. Ward, Diane M. Kaplan, Jerry Maeda, Takahiro Ponka, Prem Paw, Barry H. Lodish, Harvey F Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lodish, Harvey F. Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism. National Institutes of Health (U.S.) (P01 HL032262) 2014-04-07T14:52:05Z 2014-04-07T14:52:05Z 2013-02 2012-10 Article http://purl.org/eprint/type/JournalArticle 15504131 http://hdl.handle.net/1721.1/86052 Chen, Caiyong, Daniel Garcia-Santos, Yuichi Ishikawa, Alexandra Seguin, Liangtao Li, Katherine H. Fegan, Gordon J. Hildick-Smith, et al. “Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation.” Cell Metabolism 17, no. 3 (March 2013): 343–352. https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1016/j.cmet.2013.01.013 Cell Metabolism Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Chen, Caiyong Garcia-Santos, Daniel Ishikawa, Yuichi Seguin, Alexandra Li, Liangtao Fegan, Katherine H. Hildick-Smith, Gordon J. Shah, Dhvanit I. Cooney, Jeffrey D. Chen, Wen King, Matthew J. Yien, Yvette Y. Schultz, Iman J. Anderson, Heidi Dalton, Arthur J. Freedman, Matthew L. Kingsley, Paul D. Palis, James Hattangadi, Shilpa M. Ward, Diane M. Kaplan, Jerry Maeda, Takahiro Ponka, Prem Paw, Barry H. Lodish, Harvey F Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title | Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title_full | Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title_fullStr | Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title_full_unstemmed | Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title_short | Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation |
| title_sort | snx3 regulates recycling of the transferrin receptor and iron assimilation |
| url | http://hdl.handle.net/1721.1/86052 https://orcid.org/0000-0002-7029-7415 |
| work_keys_str_mv | AT chencaiyong snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT garciasantosdaniel snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT ishikawayuichi snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT seguinalexandra snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT liliangtao snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT fegankatherineh snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT hildicksmithgordonj snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT shahdhvaniti snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT cooneyjeffreyd snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT chenwen snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT kingmatthewj snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT yienyvettey snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT schultzimanj snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT andersonheidi snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT daltonarthurj snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT freedmanmatthewl snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT kingsleypauld snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT palisjames snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT hattangadishilpam snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT warddianem snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT kaplanjerry snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT maedatakahiro snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT ponkaprem snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT pawbarryh snx3regulatesrecyclingofthetransferrinreceptorandironassimilation AT lodishharveyf snx3regulatesrecyclingofthetransferrinreceptorandironassimilation |