All forms of life require<unk> , and yet the molecular mechanisms of Mg2+ uptake from the environment and the distribution (transport) of this vital element within the organism are only slowly being elucidated. In bacteria Mg2+ is probably mainly supplied by the CorA protein and, where the CorA protein is absent, by the MgtE protein. In yeast the initial uptake is via the Alr1p and Alr2p proteins, but at this stage the only internal Mg2+ distributing protein identified is Mrs2p. Within the protozoa only one Mg2+<unk> (XntAp) has been identified. In metazoa, Mrs2p and MgtE homologues have been identified, along with two novel Mg2+ transport systems TRPM6/TRPM7 and PCLN-1. Finally, in plants, a family of Mrs2p homologues has been identified along with another novel protein, AtMHX.
The evolution of Mg2+ transport appears to have been rather complicated. Proteins apparently based on MgtE are present in bacteria and metazoa, but are missing from fungi and plants, whilst proteins apparently related to CorA are present in all of these groups. The two active-transport<unk>  present in bacteria, MgtA and MgtB, do not appear to have any homologues in the higher organisms. There are also Mg2+ transport systems that are found only in the higher organisms.
Clearly there are a large number of proteins yet to be identified that transport Mg2+. Even in the best studied eukaryote, yeast, Borrelly have reported a Mg2+/H+ exchanger, without an associated protein, which is probably localised to the Golgi. At least one other major Mg2+<unk> in yeast still unaccounted for — that effecting Mg2+ transport into and out of the yeast vacuole. In higher, multicellular organisms it seems that many Mg2+ transporting proteins await discovery.
The CorA-domain-containing Mg2+<unk>  (CorA, Alr-like and Mrs2-like) have a similar but not identical array of affinities for divalent cations. In fact, this observation can be extended to all of the Mg2+<unk>  so far identified. This similarity suggests that the basic properties of Mg2+ strongly influence the possible mechanisms of recognition and transport. However, this observation also suggests that using other metal ions as tracers for Mg2+ uptake will not necessarily produce results comparable to the<unk> s ability to transport Mg2+. Ideally, Mg2+ should be measured directly.
In a world where 28Mg2+ is practically unobtainable, much of the old data will need to be reinterpreted in terms of new tools for measuring Mg2+ transport, if different<unk>  are to be compared directly. The pioneering work of Kolisek and Froschauer using mag-fura 2 has shown that free Mg2+ can be reliably measured in vivo in some systems. By returning to the analysis of CorA with this new tool, we have gained an important baseline for the analysis of new Mg2+ transport systems as they are discovered. However, it is important that the amount of<unk> present in the membrane is accurately determined if comparisons of transport capability are to be made. This bacterial system might also be able to provide some utility for the analysis of eukaryotic Mg2+ transport proteins. However, the differences in biological systems between prokaryotes and eukaryotes will have to be considered as part of any experiment.
Comparing the functions of the characterised Mg2+ transport proteins is currently almost impossible. The proteins have been investigated in different biological systems using different methodologies and technologies. Finding a system where all the proteins can be compared directly would be a major advance. If the proteins could be shown to be functional in bacteria (S. typhimurium) then a combination of the techniques of mag-fura 2, quantification of protein in the envelope membrane, and structure of the proteins (X-ray crystal or cryo-TEM) might allow the determination of the basic mechanisms involved in the recognition and transport of the Mg2+ ion. However, perhaps the best advance would be the development of methods allowing the measurement of the protein’s function in the patch-clamp system using artificial membranes.
Magnesium transporters
Sodium calcium exchanger
Light-gated ion channel
Cyclic nucleotide-gated ion channel
Chloride channel
Voltage-gated proton channels
Calcium channel
Ion transporter