Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 343-352 |
| Number of pages | 10 |
| Journal | Cell metabolism |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 5 2013 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Physiology
- Molecular Biology
- Cell Biology
Cite this
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.; Lodish, Harvey F.; Ward, Diane M.; Kaplan, Jerry; Maeda, Takahiro; Ponka, Prem; Paw, Barry H.
In: Cell metabolism, Vol. 17, No. 3, 05.03.2013, p. 343-352.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Snx3 regulates recycling of the transferrin receptor and iron assimilation
AU - Chen, Caiyong
AU - Garcia-Santos, Daniel
AU - Ishikawa, Yuichi
AU - Seguin, Alexandra
AU - Li, Liangtao
AU - Fegan, Katherine H.
AU - Hildick-Smith, Gordon J.
AU - Shah, Dhvanit I.
AU - Cooney, Jeffrey D.
AU - Chen, Wen
AU - King, Matthew J.
AU - Yien, Yvette Y.
AU - Schultz, Iman J.
AU - Anderson, Heidi
AU - Dalton, Arthur J.
AU - Freedman, Matthew L.
AU - Kingsley, Paul D.
AU - Palis, James
AU - Hattangadi, Shilpa M.
AU - Lodish, Harvey F.
AU - Ward, Diane M.
AU - Kaplan, Jerry
AU - Maeda, Takahiro
AU - Ponka, Prem
AU - Paw, Barry H.
PY - 2013/3/5
Y1 - 2013/3/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875382908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875382908&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2013.01.013
DO - 10.1016/j.cmet.2013.01.013
M3 - Article
C2 - 23416069
AN - SCOPUS:84875382908
VL - 17
SP - 343
EP - 352
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -