Signal Sequence Cleavage and Plasma Membrane Targeting of the Retinal Rod NCKX1 and Cone NCKX2 Na<sup>+</sup>/Ca<sup>2+</sup>−K<sup>+</sup>Exchangers
Bibliographic record
Abstract
Retinal rod and cone photoreceptors express two distinct Na(+)/Ca(2+)-K(+) exchanger (NCKX) gene products. Both the rod NCKX1 and cone NCKX2 are polytopic membrane proteins thought to contain a putative cleavable signal peptide. A cleavable signal peptide is unusual for plasma membrane proteins; moreover, predictive algorithms suggest the presence of a cleavable signal peptide for all rod NCKX1 proteins and a noncleavable signal anchor for the cone NCKX2 proteins. In this study we have placed a peptide tag at different positions of the NCKX sequence to examine whether the putative signal sequence is indeed cleaved in either NCKX1 or NCKX2 proteins expressed in heterologous systems. The signal peptide was found to be, at least in part, cleaved in dolphin rod NCKX1 and in chicken and human cone NCKX2 expressed in HEK293 cells; no signal peptide cleavage was observed for chicken rod NCKX1 despite the fact that the SignalP predictive algorithm assigned this sequence to have the highest likelihood for a cleavable signal peptide among the three NCKX sequences tested here. For the two NCKX proteins that contained a cleavable signal peptide, only cleaved NCKX protein was found in the plasma membrane of HEK293 cells. Deletion of the signal sequence in both dolphin rod NCKX1 or cone NCKX2 did not affect NCKX protein synthesis but did disrupt plasma membrane targeting as judged from abolition of NCKX function and from lack of surface biotinylation. These results are consistent with delayed signal peptide cleavage for the rod and cone NCKX proteins.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".