Distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, synaptic localization, and dimerization
Bibliographic record
Abstract
Synaptic adhesion molecules are essential components of the synapse, yet the diversity of these molecules and their associated functions remain to be fully characterized. Extracellular leucine rich repeat and fibronectin type III domain containing 1 (ELFN1) is a postsynaptic adhesion molecule in the brain that has been increasingly implicated in human neurological disease. ELFN1 is best known for trans-synaptically modulating group III metabotropic glutamate receptors (mGluRs). However, little is known about ELFN1 organization and regulation, which likely govern and precede its ultimate trans-synaptic engagement with group III mGluRs. Herein, we report that the intracellular ELFN1 domain controls membrane trafficking and post-synaptic localization of ELFN1. We pinpoint a ∼30 amino acid juxtamembranous region required for membrane-targeting and discover that ELFN1 exists as an obligate homodimer prior to its trafficking to the membrane. We determine that ELFN1 homodimerization is not appreciably affected by the intracellular region and instead utilizes the extracellular leucine rich repeats (LRR) domain. We find that a single membrane-targeting motif located in one protomer is sufficient for effective trafficking of the ELFN1 homodimer. We further demonstrate that the closest ELFN1 homolog, synaptic adhesion molecule ELFN2, exhibits similar properties and participates in heterodimerization with ELFN1. This establishes distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, post-synaptic localization, and dimerization while indicating conservation of the mechanisms across the ELFN subfamily of cell adhesion molecules.
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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) | 0.000 | 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) | 0.001 | 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 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".