Transferrin receptor 1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene.{{cite journal | vauthors = Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M | title = Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 7 | pages = 4515–9 | date = July 1981 | pmid = 6270680 | pmc = 319822 | doi = 10.1073/pnas.78.7.4515 | bibcode = 1981PNAS...78.4515S | doi-access = free }}{{cite journal | vauthors = Rabin M, McClelland A, Kühn L, Ruddle FH | title = Regional localization of the human transferrin receptor gene to 3q26.2----qter | journal = American Journal of Human Genetics | volume = 37 | issue = 6 | pages = 1112–6 | date = November 1985 | pmid = 3002171 | pmc = 1684729 }} TfR1 is required for iron import from transferrin into cells by endocytosis.{{cite journal | vauthors = Aisen P | title = Transferrin receptor 1 | journal = The International Journal of Biochemistry & Cell Biology | volume = 36 | issue = 11 | pages = 2137–43 | date = November 2004 | pmid = 15313461 | doi = 10.1016/j.biocel.2004.02.007 }}{{cite journal | vauthors = Moos T | title = Brain iron homeostasis | journal = Danish Medical Bulletin | volume = 49 | issue = 4 | pages = 279–301 | date = November 2002 | pmid = 12553165 }}

Structure and function

File:Cellular iron homeostasis.png.]]

TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis.{{cite journal | vauthors = Speeckaert MM, Speeckaert R, Delanghe JR | title = Biological and clinical aspects of soluble transferrin receptor | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 47 | issue = 5–6 | pages = 213–28 | date = December 2010 | pmid = 21391831 | doi = 10.3109/10408363.2010.550461 | s2cid = 25425279 }}

Clinical significance

TfR1 as a potential new target in cases of human leukemia & lymphoma. InatherYs, in Évry, France, developed a candidate drug, INA01 antibody (anti-CD71) that showed efficacy in pre-clinical studies in the therapy of two incurable orphan oncohematological diseases: the adult T cell leukemia (ATLL) caused by HTLV-1 and the Mantle cell lymphoma (MCL).{{citation needed|date=February 2013}}

TfR1 expressed on the endothelial cells of the blood-brain barrier (BBB) is used also in preclinical research to allow the delivery of large molecules including antibodies into the brain.{{cite journal | vauthors = Johnsen KB, Burkhart A, Thomsen LB, Andresen TL, Moos T | title = Targeting the transferrin receptor for brain drug delivery | journal = Progress in Neurobiology | volume = 181 | pages = 101665 | date = October 2019 | pmid = 31376426 | doi = 10.1016/j.pneurobio.2019.101665 | s2cid = 199405122 | url = https://vbn.aau.dk/ws/files/308691033/1_s2.0_S0301008219301340_main.pdf }} Some of the TfR1 targeting antibodies have been shown to cross the blood-brain barrier, without interfering with the uptake of iron. Amongst those are the mouse anti rat-TfR antibody OX26{{cite journal | vauthors = Pardridge WM, Buciak JL, Friden PM | title = Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 259 | issue = 1 | pages = 66–70 | date = October 1991 | pmid = 1920136 }} and the rat anti mouse-TfR antibody 8D3.{{cite journal | vauthors = Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM | title = Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 292 | issue = 3 | pages = 1048–52 | date = March 2000 | pmid = 10688622 }} The affinity of the antibody-TfR interaction seems to be important determining the success of transcytotic transport over endothelial cells of the BBB. Monovalent TfR interaction favors BBB transport due to altered intracellular sorting pathways. Avidity effects of bivalent interactions redirecting transport to the lysosome.{{cite journal | vauthors = Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, Rueger P, Stracke JO, Lau W, Tissot AC, Loetscher H, Ghosh A, Freskgård PO | display-authors = 6 | title = Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle | journal = Neuron | volume = 81 | issue = 1 | pages = 49–60 | date = January 2014 | pmid = 24411731 | doi = 10.1016/j.neuron.2013.10.061 | doi-access = free }} Also, reducing TfR binding affinity directly promote dissociation from the TfR which increase brain parenchymal exposure of the TfR binding antibody.{{cite journal | vauthors = Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, Atwal J, Elliott JM, Prabhu S, Watts RJ, Dennis MS | display-authors = 6 | title = Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target | journal = Science Translational Medicine | volume = 3 | issue = 84 | pages = 84ra44 | date = May 2011 | pmid = 21613623 | doi = 10.1126/scitranslmed.3002230 | s2cid = 34161824 }}

Interactions

TfR1 has been shown to interact with GABARAP{{cite journal | vauthors = Green F, O'Hare T, Blackwell A, Enns CA | title = Association of human transferrin receptor with GABARAP | journal = FEBS Letters | volume = 518 | issue = 1–3 | pages = 101–6 | date = May 2002 | pmid = 11997026 | doi = 10.1016/S0014-5793(02)02655-8 | s2cid = 29391940 | url = https://escholarship.org/content/qt75g9j0p1/qt75g9j0p1.pdf?t=ntzy5g | doi-access = free }} and HFE.{{cite journal | vauthors = Feder JN, Penny DM, Irrinki A, Lee VK, Lebrón JA, Watson N, Tsuchihashi Z, Sigal E, Bjorkman PJ, Schatzman RC | display-authors = 6 | title = The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 4 | pages = 1472–7 | date = February 1998 | pmid = 9465039 | pmc = 19050 | doi = 10.1073/pnas.95.4.1472 | bibcode = 1998PNAS...95.1472F | doi-access = free }}{{cite journal | vauthors = West AP, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ | title = Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE | journal = The Journal of Biological Chemistry | volume = 275 | issue = 49 | pages = 38135–8 | date = December 2000 | pmid = 11027676 | doi = 10.1074/jbc.C000664200 | doi-access = free }}

Immunostain marker

CD71 is a robust immunohistochemistry marker for chorionic villi, especially in necrotic specimens. Among white blood cells and precursors, CD71 is expressed only by erythroid precursors within the normal hematopoietic marrow and spleen, in contrast to glycophorin that marks all types of red blood cells.{{cite web |url= https://www.pathologyoutlines.com/topic/cdmarkerscd71.html |title=CD71| vauthors = Morelli L, Luchini C | date = 14 May 2021 | orig-date = 16 November 2020 |website= Pathology Outlines}}

References

External links

{{PDBe-KB2|P02786|Human Transferrin receptor protein 1}}

Category:Iron metabolism

Category:Clusters of differentiation

Category:Transferrins