Degradation of the non-palmitoylated invertebrate visual guanine-nucleotide binding protein, iG<sub>q</sub>α(C3,4A), by the ubiquitin-proteasomal pathway is regulated by its activation and translocation to the cytoplasm
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Bibliographic record
Abstract
Light-dependent translocation of invertebrate visual guanine-nucleotide binding protein, iGq alpha, from rhabdomeric membranes to the cytoplasm is one of many mechanisms that contribute to light adaptation in the invertebrate eye. We have previously cloned iGq alpha from a Loligo pealei photoreceptor cDNA library and shown that when expressed in HEK 293T cells it is palmitoylated. In this study we compared the activation, cytoplasmic translocation, and turnover of iGq alpha with that of a non-palmitoylated mutant, iGq alpha(C3,4A). In the HEK 293T cells, muscarinic M1 receptors coupled equally well to iGq alpha and iGq alpha(C3,4A) to activate phospholipase C. Activation of iGq alpha(C3,4A), but not iGq alpha, induced translocation of the alpha subunit from the membrane to cytosol with rapid degradation of the soluble protein resulting in a decreased half-life for iGq alpha(C3,4A) of 10 hours compared to 20 hours for iGq alpha. Degradation of iGq alpha(C3,4A) was inhibited by proteasomal inhibitors but not by inhibitors of lysosomal proteases or calpain. The presence of the proteasomal inhibitor led to the accumulation of polyubiquitinated species of either iGq alpha or iGq alpha(C3,4A). Our results suggest that palmitoylation of iGq alpha is required to maintain membrane association of the protein in its active conformation, and whereas membrane-bound and soluble iGq alpha can be polyubiquitinated, membrane association protects the protein from rapid degradation by the proteasomal pathway.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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 it