Zinc transporter ZIP8 is a

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...

symporter A symporter is an integral membrane protein that is involved in the transport of two (or more) different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across th ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

which in humans is encoded by the ''SLC39A8''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

This

transmembrane protein A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

is responsible for the influx of

zinc Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...

manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

, and

cadmium Cadmium is a chemical element; it has chemical symbol, symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12 element, group 12, zinc and mercury (element), mercury. Like z ...

. ZIP8 is distributed among the

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

, and

yolk sac The yolk sac is a membranous wikt:sac, sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac' ...

during development. 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 The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

. Cardiac development is a zinc-dependent event. Beginning around mouse E8.0, the heart is in a tubular form with an outer

myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

layer and an inner

endocardium The endocardium (: endocardia) is the innermost layer of tissue that lines the chambers of the heart. Its cells are embryologically and biologically similar to the endothelial cells that line blood vessels. The endocardium also provides prot ...

layer, separated by cardiac jelly. As development continues, trabeculation, the

protrusion Motion, the process of movement, is described using specific anatomical terms. Motion includes movement of organs, joints, limbs, and specific sections of the body. The terminology used describes this motion according to its direction relative ...

cardiomyocytes Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

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 A trabecula (: trabeculae, from Latin for 'small beam') is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has a ...

then collapse into the ventricular wall in a process known as compaction.

Cardiomyocyte Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

differentiation, proliferation, and trabeculae patterning is regulated through

Notch 1 Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor (biochemistry), receptor. Function This gene encodes a member of the Notch signaling, No ...

signaling A signal is both the process and the result of transmission of data over some media accomplished by embedding some variation. Signals are important in multiple subject fields including signal processing, information theory and biology. ...

, which is upregulated by the ECM.

ADAMTS ADAMTS (short for a disintegrin and metalloproteinase with thrombospondin motifs) is a family of multidomain extracellular protease enzymes. 19 members of this family have been identified in humans, the first of which, ADAMTS1, was described in 1997 ...

1, 5, 7, 15, and 19 are zinc

metalloenzymes Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-binding protein domains al ...

responsible for degrading the ECM prior to compaction. 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 Cardiomyocyte proliferation refers to the ability of cardiac muscle cells to progress through the cell cycle and continue to divide. Traditionally, cardiomyocytes were believed to have little to no ability to proliferate and regenerate after birth. ...

through

BMP10 Bone morphogenetic protein 10 (BMP10) is a protein that in humans is encoded by the ''BMP10'' gene. BMP10 is a polypeptide belonging to the TGF-β superfamily of proteins. It is a novel protein that, unlike most other BMP's, is likely to be in ...

, hypertrabeculation through the upregulation of Notch1, and ventricular non-compaction due to the persistence of the ECM.

References

{{reflist Genes Solute carrier family