Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

被引：91

作者：

Chen, Caiyong ^{[1
]}

Garcia-Santos, Daniel ^{[2
,3
]}

Ishikawa, Yuichi ^{[1
]}

Seguin, Alexandra ^{[4
]}

Li, Liangtao ^{[4
]}

Fegan, Katherine H. ^{[5
]}

Hildick-Smith, Gordon J. ^{[1
]}

Shah, Dhvanit I. ^{[1
]}

Cooney, Jeffrey D. ^{[1
]}

Chen, Wen ^{[1
]}

King, Matthew J. ^{[1
]}

Yien, Yvette Y. ^{[1
]}

Schultz, Iman J. ^{[1
]}

Anderson, Heidi ^{[1
]}

Dalton, Arthur J. ^{[1
]}

Freedman, Matthew L. ^{[6
]}

Kingsley, Paul D. ^{[5
]}

Palis, James ^{[5
]}

Hattangadi, Shilpa M. ^{[1
,7
,8
,9
,10
]}

Lodish, Harvey F. ^{[9
,10
]}

Ward, Diane M. ^{[4
]}

Kaplan, Jerry ^{[4
]}

Maeda, Takahiro ^{[1
]}

Ponka, Prem ^{[2
,3
]}

Paw, Barry H. ^{[1
,7
,8
]}

机构：

[1] Harvard Univ, Sch Med, Dept Med, Div Hematol,Brigham & Womens Hosp, Boston, MA 02115 USA

[2] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3G 1Y6, Canada

[3] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada

[4] Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84312 USA

[5] Univ Rochester, Sch Med & Dent, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA

[6] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Med, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA

[9] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[10] MIT, Cambridge, MA 02142 USA

来源：

CELL METABOLISM | 2013年 / 17卷 / 03期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

ERYTHROID-DIFFERENTIATION; GENE; METABOLISM; LOCI; ERYTHROPOIESIS; MICROPHTHALMIA; TRAFFICKING; PROGNATHISM; REPRESSION; TRANSPORT;

D O I：

10.1016/j.cmet.2013.01.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：343 / 352

页数：10

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