Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

被引：95

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：

加拿大健康研究院; 美国国家卫生研究院;

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

共 53 条

[31] Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol [J].

Richardson, Des R. ;

Lane, Darius J. R. ;

Becker, Erika M. ;

Huang, Michael L. -H. ;

Whitnall, Megan ;

Rahmanto, Yohan Suryo ;

Sheftel, Alex D. ;

Ponka, Prem .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (24) :10775-10782

[32] Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis [J].

Schranzhofer, Matthias ;

Schifrer, Manfred ;

Cabrera, Javier Antonio ;

Kopp, Stephan ;

Chiba, Peter ;

Beug, Hartmut ;

Muellner, Ernst W. .

BLOOD, 2006, 107 (10) :4159-4167

[33] Iron and Porphyrin Trafficking in Heme Biogenesis [J].

Schultz, Iman J. ;

Chen, Caiyong ;

Paw, Barry H. ;

Hamza, Iqbal .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (35) :26753-26759

[34] Mitoferrin is essential for erythroid iron assimilation [J].

Shaw, GC ;

Cope, JJ ;

Li, LT ;

Corson, K ;

Hersey, C ;

Ackermann, GE ;

Gwynn, B ;

Lambert, AJ ;

Wingert, RA ;

Traver, D ;

Trede, NS ;

Barut, BA ;

Zhou, Y ;

Minet, E ;

Donovan, A ;

Brownlie, A ;

Balzan, R ;

Weiss, MJ ;

Peters, LL ;

Kaplan, J ;

Zon, LI ;

Paw, BH .

NATURE, 2006, 440 (7080) :96-100

[35] ABC-me: a novel mitochondrial transporter induced by GATA-1 during erythroid differentiation [J].

Shirihai, OS ;

Gregory, T ;

Yu, CN ;

Orkin, SH ;

Weiss, MJ .

EMBO JOURNAL, 2000, 19 (11) :2492-2502

[36] A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium [J].

Soranzo, Nicole ;

Spector, Tim D. ;

Mangino, Massimo ;

Kuehnel, Brigitte ;

Rendon, Augusto ;

Teumer, Alexander ;

Willenborg, Christina ;

Wright, Benjamin ;

Chen, Li ;

Li, Mingyao ;

Salo, Perttu ;

Voight, Benjamin F. ;

Burns, Philippa ;

Laskowski, Roman A. ;

Xue, Yali ;

Menzel, Stephan ;

Altshuler, David ;

Bradley, John R. ;

Bumpstead, Suzannah ;

Burnett, Mary-Susan ;

Devaney, Joseph ;

Doering, Angela ;

Elosua, Roberto ;

Epstein, Stephen E. ;

Erber, Wendy ;

Falchi, Mario ;

Garner, Stephen F. ;

Ghori, Mohammed J. R. ;

Goodall, Alison H. ;

Gwilliam, Rhian ;

Hakonarson, Hakon H. ;

Hall, Alistair S. ;

Hammond, Naomi ;

Hengstenberg, Christian ;

Illig, Thomas ;

Koenig, Inke R. ;

Knouff, Christopher W. ;

McPherson, Ruth ;

Melander, Olle ;

Mooser, Vincent ;

Nauck, Matthias ;

Nieminen, Markku S. ;

O'Donnell, Christopher J. ;

Peltonen, Leena ;

Potter, Simon C. ;

Prokisch, Holger ;

Rader, Daniel J. ;

Rice, Catherine M. ;

Roberts, Robert ;

Salomaa, Veikko .

NATURE GENETICS, 2009, 41 (11) :1182-U38

[37]

STAINIER DYR, 1995, DEVELOPMENT, V121, P3141

[38] Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome [J].

Strochlic, Todd I. ;

Schmiedekamp, Briana C. ;

Lee, Jacqueline ;

Katzmann, David J. ;

Burd, Christopher G. .

MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (11) :4694-4706

[39] Grd19/Snx3p functions as a cargo-specic adapter for retromer-dependent endocytic recycling [J].

Strochlic, Todd I. ;

Setty, Thanuja Gangi ;

Sitaram, Anand ;

Burd, Christopher G. .

JOURNAL OF CELL BIOLOGY, 2007, 177 (01) :115-125

[40] A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells [J].

Tallack, Michael R. ;

Whitington, Tom ;

Yuen, Wai Shan ;

Wainwright, Elanor N. ;

Keys, Janelle R. ;

Gardiner, Brooke B. ;

Nourbakhsh, Ehsan ;

Cloonan, Nicole ;

Grimmond, Sean M. ;

Bailey, Timothy L. ;

Perkins, Andrew C. .

GENOME RESEARCH, 2010, 20 (08) :1052-1063

← 1 2 3 4 5 6 →