Expression and proteomic analysis of KlFlA/25B in hereditary sensory and autonomic neuropathies type ll
Bibliographic record
Abstract
Hereditary sensory and autonomic neuropathies (HSANs) form a group of rare disorders that are characterized by variable sensory and autonomic dysfunctions. HSAN type II (HSAN-II) is a particularly debilitating subtype in which recurrent injuries lead to ulceration, infection, amputation, and death. Despite the significant suffering this disease inflicts, no treatment can yet be offered and much remains to be understood about the pathology underlying HSAN-II. The first cluster of HSAN-II cases was reported in eastern Canada, with half the cases representing patients of French-Canadian descent. This project focuses specifically on answering fundamental questions regarding the molecular pathophysiology of HSAN-II, though the findings could have an important impact on our understanding both of other neuropathies and of normal nerve cell functioning.Recently the identification of deleterious variations in two genes provided key insights about the genetic architecture and elements underlying HSAN-II. The team of Dr. Guy Rouleau reported truncating mutations in a nervous-tissue-specific exon (HSN2 exon) of the WNK1 gene (lysine deficient protein kinase 1). The WNK1 isoform containing the alternatively spliced HSN2 exon was termed the WNK1/HSN2 isoform, and was found to directly interact with a particular isoform of another HSAN-II causative gene, KIF1A. The HSAN-II-causing KIF1A isoform is named KIF1A/25B as disease-causing mutations were exclusively found in the alternatively spliced exon "25B". This study focuses on assessing the function of the protein domain encoded by exon 25B through a profiling of its interacting partners; specifically focusing on KIF1A/25B implication in axonal trafficking and slightly investigating the expression profile of KIF1A/25B isoform.Here, we identified a list of protein interactors of KIF1A/25B through co-immunoprecipitation (co-IP) followed by mass spectrometry. We confirmed KIF1A-SYT11 interaction via co-IP; however, we were unable to confirm that this interaction is unique to exon 25B. SYT11-KIF1A interaction could suggests that KIF1A is a transit system through which SYT11 traffics within the cells and locates at axonal terminal where it plays a role in establishing balanced endo-exocytosis and sustained neurotransmission. Moreover, we found that KIF1A/25B is mainly present in nervous tissue and absent in non-nervous tissues.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 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".