Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with Veli3 at distinct intercellular junctions of the neurosensory retina
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Bibliographic record
Abstract
MPP4 and MPP5 are closely related members of the p55-subfamily of membrane-associated guanylate kinases (MAGUKs) known to mediate the assembly of protein complexes at the plasma membrane of cell-cell junctions. Both MPP4 and MPP5 have been implicated in retinal function; however, their specific roles in the cellular mechanisms underlying vision are largely unknown. Here, we generated specific poly- and monoclonal antibodies against the two proteins and show that MPP4 and MPP5 are localized at distinct sites of cell-cell contact in the mouse retina. While MPP4 is a component of the synaptic terminals of photoreceptors, MPP5 exclusively localizes to apical membrane domains of the outer limiting membrane (OLM) junctions. The vertebrate homologs of Caenorhabditis elegans lin-7, Veli1, -2, and -3, have previously been identified as putative binding partners of MPP5. In this study, we show that MPP4 directly interacts with the Veli proteins via L27 heterodimerization in vitro. In addition, two of the three Veli isoforms, Veli1 and -3, are demonstrated to be expressed in the mouse retina. Immunofluorescence microscopy reveals extensive colocalization of Veli3 with both MPP4 and MPP5. This association of Veli3 with either MPP4 or MPP5 suggests that the MAGUKs recruit Veli3 and its binding partners to different cellular regions of the retina where they may participate in the organization of specialized intercellular junctions.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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