Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility
Bibliographic record
Abstract
Infertility is a growing concern in modern society, with 30% of cases being due to male factors, namely reduced sperm concentration, decreased motility and abnormal morphology. Sperm cells are highly compartmentalized, almost devoid of transcription and translation consequently processes such as protein phosphorylation provide a key general mechanism for regulating vital cellular functions, more so than for undifferentiated cells. Reversible protein phosphorylation is the principal mechanism regulating most physiological processes in eukaryotic cells. To date, hundreds of protein kinases have been identified, but significantly fewer phosphatases (PPs) are responsible for counteracting their action. This discrepancy can be explained in part by the mechanism used to control phosphatase activity, which is based on regulatory interacting proteins. This is particularly true for PP1, a major serine/threonine-PP, for which >200 interactors (PP1 interacting proteins-PIPs) have been indentified that control its activity, subcellular location and substrate specificity. For PP1, several isoforms have been described, among them PP1γ2, a testis/sperm-enriched PP1 isoform. Recent findings support our hypothesis that PP1γ2 is involved in the regulation of sperm motility. This review summarizes the known sperm-specific PP1-PIPs, involved in the acquisition of mammalian sperm motility. The complexes that PP1 routinely forms with different proteins are addressed and the role of PP1/A-kinase anchoring protein complexes in sperm motility is considered. Furthermore, the potential relevance of targeting PP1-PIPs complexes to infertility diagnostics and therapeutics as well as to male contraception is also discussed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".