{{Short description|Protein found in humans}} {{Use dmy dates|date=April 2019}} {{infobox gene}} '''Zinc transporter ZIP8''' is a cation/bicarbonate symporter protein which in humans is encoded by the ''SLC39A8'' gene.<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/64116 |title=SLC39A8 solute carrier family 39 member 8 [Homo sapiens (human)] – Gene – NCBI |website=www.ncbi.nlm.nih.gov |publisher=National Center for Biotechnology Information, U.S. National Library of Medicine |access-date=19 April 2019}}</ref><ref>{{cite web | vauthors = Park JH, Hogrebe M, Grüneberg M |url=https://www.researchgate.net/publication/322251760 |title=SLC39A8 deficiency is a novel treatable disorder of manganese metabolism and glycosylation |website=ResearchGate |access-date=19 April 2019}}</ref><ref name="Gálvez-Peralta_2012">{{cite journal | vauthors = Gálvez-Peralta M, He L, Jorge-Nebert LF, Wang B, Miller ML, Eppert BL, Afton S, Nebert DW | title = ZIP8 zinc transporter: indispensable role for both multiple-organ organogenesis and hematopoiesis in utero | journal = PLOS ONE | volume = 7 | issue = 5 | article-number = e36055 | date = 2012 | pmid = 22563477 | pmc = 3341399 | doi = 10.1371/journal.pone.0036055 | bibcode = 2012PLoSO...736055G | doi-access = free }}</ref>
== Function ==
This transmembrane protein is responsible for the influx of zinc, manganese, and cadmium.<ref name="Wang_2011">{{cite journal | vauthors = Wang B, He L, Dong H, Dalton TP, Nebert DW | title = Generation of a Slc39a8 hypomorph mouse: markedly decreased ZIP8 Zn<sup>2+</sup>/(HCO<sub>3</sub><sup>−</sup>)<sub>2</sub> transporter expression | journal = Biochemical and Biophysical Research Communications | volume = 410 | issue = 2 | pages = 289–94 | date = July 2011 | pmid = 21658371 | pmc = 3136049 | doi = 10.1016/j.bbrc.2011.05.134 }}</ref> ZIP8 is distributed among the embryo, placenta, and yolk sac during development.<ref name="Chen_2018">{{cite journal | vauthors = Chen J, Gálvez-Peralta M, Zhang X, Deng J, Liu Z, Nebert DW | title = In utero gene expression in the Slc39a8(neo/neo) knockdown mouse | journal = Scientific Reports | volume = 8 | issue = 1 | page = 10703 | date = July 2018 | pmid = 30013175 | pmc = 6048144 | doi = 10.1038/s41598-018-29109-y | bibcode = 2018NatSR...810703C }}</ref> Within the embryo, the concentration of ZIP8 is highest during the developmental period of different organ systems, specifically the heart where is it localized in the endothelial cells. Cardiac development is a zinc-dependent event. Beginning around mouse E8.0, the heart is in a tubular form with an outer myocardium layer and an inner endocardium layer, separated by cardiac jelly.<ref name="Lin_2018b">{{cite journal | vauthors = Lin W, Li D | title = Zinc and Zinc Transporters: Novel Regulators of Ventricular Myocardial Development | journal = Pediatric Cardiology | volume = 39 | issue = 5 | pages = 1042–1051 | date = June 2018 | pmid = 29536133 | doi = 10.1007/s00246-018-1859-y | s2cid = 3861584 }}</ref> As development continues, trabeculation, the protrusion of cardiomyocytes into the cardiac jelly, begins and facilitates nutrient and oxygen exchange prior to the establishment of coronary vessels. Simultaneous with coronary circulation development, the trabeculae then collapse into the ventricular wall in a process known as compaction. Cardiomyocyte differentiation, proliferation, and trabeculae patterning is regulated through Notch 1 signaling, which is upregulated by the ECM. ADAMTS 1, 5, 7, 15, and 19 are zinc metalloenzymes responsible for degrading the ECM prior to compaction.<ref name="Lin_2018a">{{cite journal | vauthors = Lin W, Li D, Cheng L, Li L, Liu F, Hand NJ, Epstein JA, Rader DJ | title = Zinc transporter Slc39a8 is essential for cardiac ventricular compaction | journal = The Journal of Clinical Investigation | volume = 128 | issue = 2 | pages = 826–833 | date = February 2018 | pmid = 29337306 | pmc = 5785267 | doi = 10.1172/JCI96993 }}</ref> Many studies have analyzed the effects of Slc39a8-/- on fetal heart development and have shown a decrease in zinc influx leading to an increase in cardiomyocyte proliferation through BMP10, hypertrabeculation through the upregulation of Notch1, and ventricular non-compaction due to the persistence of the ECM.
== References == {{reflist}}
Category:Genes Category:Solute carrier family