Aim: 

Aquaporin-4 (AQP4) is expressed as heterotetramers made of two isoforms called AQP4-M23 and AQP4-M1. Freeze-fracture electron microscopy (FFEM) indicates that these tetramers further aggregate to form Orthogonal Arrays of Particles (OAPs) whose dimension is depending on the ratio M1/M23. We tested the hypothesis that the cell can produce the M23 isoform and thus regulate the M1/M23 expression ratio by the M1 mRNA through a mechanism of leaky scanning.

Methods and Results: 

To this purpose, using mammalian cells transfected with M1 and/or M23 coding sequence we observed by immunoblotting the presence of the M23 isoform. By BN-SDS/PAGE and immunofluorescence we observed the formation of typical OAP in cells transfected with the M1-cds. The mutation of the second in-frame methionine (M1-AQP4M23I) prevented the expression of the M23 isoform and the formation of OAPs. Based on these data we propose that the leaky scanning mechanism exists as translational mechanism in the expression of the AQP4 gene.

Conclusion: 

These findings may have important implications in the cell physiology for the tissue specific regulation of OAP size and also in pathologies in which an altered M1/M23 ratio affect OAP formation.