An iron delivery pathway mediated by a lipocalin.
Despite the critical need for iron in many cellular reactions, deletion of the transferrin pathway does not block organogenesis, suggesting the presence of alternative methods to deliver iron. We show that a member of the lipocalin superfamily (24p3/Ngal) delivers iron to the cytoplasm where it activates or represses iron-responsive genes. Iron unloading depends on the cycling of 24p3/Ngal through acidic endosomes, but its pH sensitivity and its subcellular targeting differed from transferrin. Indeed, during the conversion of mesenchyme into epithelia (where we discovered the protein), 24p3/Ngal and transferrin were endocytosed by different cells that characterize different stages of development, and they triggered unique responses. These studies identify an iron delivery pathway active in development and cell physiology.
Yang
Jun
J
College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Goetz
David
D
Li
Jau Yi
JY
Wang
Wenge
W
Mori
Kiyoshi
K
Setlik
Daria
D
Du
Tonggong
T
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Strong
Roland
R
Barasch
Jonathan
J
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015513:Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D016622:Silver Staining; D013347:Subcellular Fractions; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
D000209:Acute-Phase Proteins; D015513:Oncogene Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron