Title : Topology of the retinal cone
NCKX2 Na/Ca-K exchanger
Abstract :
- The Na/Ca-K exchanger ( NCKX ) is a polytopic membrane protein that plays a critical role in Ca(2 +) homeostasis in retinal rod and cone photoreceptors
- The NCKX1 isoform is found in rods, while the NCKX2 isoform is found in cones, in retinal ganglion cells, and in various parts of the brain
- The topology of the Na/Ca-K exchanger is thought to consist of two large hydrophilic loops and two sets of transmembrane spanning segments (TMs)
- The first large hydrophilic loop is located extracellularly at the N-terminus; the other is cytoplasmic and separates the two sets of TMs
- The TMs consist of either five and five membrane spanning helices or five and six membrane spanning helices, depending upon the predictive algorithm used
- Little specific information is yet available on the orientation of the various membrane spanning helices and the localization of the short loops connecting these helices
- In this study, we have determined which of the connecting loops are exposed to the extracellular milieu using two different methods: accessibility of substituted cysteine residues and insertion of N-glycosylation sites
- The two methods resulted in a consistent NCKX topology in which the two sets of TMs each contain five membrane spanning helices
- Our new model places what was previously membrane spanning helix six in the cytoplasm, which places the C-terminus on the extracellular surface
- Surprisingly, this NCKX topology model is different from the current NCX topology model with respect to the C-terminal three membrane helices