Abstract
The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.
Highlights
OCTN1 (SLC22A4) is the first member of the human Novel Organic Cation Transporters small subfamily, which is part of the larger SLC22 family
OCTN1 is expressed in the brain in neural stem cells, neurons, and in microglia, the “macrophages” of the brain [46], at much higher levels in neural stem cells compared with other Organic Cation Transporters, OCTs
This comprehensive approach led to the identification of a wider functional subgroup including OCTN1 and OCTN2, together with the Slc22a21 gene coding for OCTN3, which has been lost in humans, and other transporters considered as OCTN-related
Summary
OCTN1 (SLC22A4) is the first member of the human Novel Organic Cation Transporters small subfamily, which is part of the larger SLC22 family. These transporters appeared in evolution with vertebrates, being interesting for human metabolism [1]. Besides terrestrial animals closer to humans, OCTN1 is present in aquatic species such as Danio rerio (zebra fish) [2] and rainbow trout [3] In the latter species, the capacity of OCTN1 in mediating ergothioneine transport has been tested, even though no information on a possible physiological function of ergothioneine in salmonids is available [3]. Such as choline, spermine, etc. (see Table 1 and Figure 1a) [7,12,13,14]
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