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Record W3208816664 · doi:10.1016/j.celrep.2021.109940

Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors

2021· article· en· W3208816664 on OpenAlexafffund
Jing Wang, Neelima Vaddadi, Joseph S. Pak, Yeonwoo Park, Sabrina Quilez, Christina Roman, Émilie Dumontier, Joseph W. Thornton, Jean‐François Cloutier, Engin Özkan

Bibliographic record

VenueCell Reports · 2021
Typearticle
Languageen
FieldNeuroscience
TopicOlfactory and Sensory Function Studies
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersSLAC National Accelerator LaboratoryNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchOffice of ScienceBiological and Environmental ResearchSamsungDirectorate for Biological SciencesNational Institutes of HealthHebrew University of JerusalemArgonne National LaboratoryU.S. Department of EnergyMcGill UniversityAcademy of Pharmaceutical SciencesBasic Energy SciencesNatural Sciences and Engineering Research Council of CanadaUniversity of Texas Southwestern Medical Center
KeywordsOlfactory bulbSensory systemNeuroscienceAxonReceptorBiologySensory neuronNeuronOlfactory systemCell biologyCentral nervous systemBiochemistry

Abstract

fetched live from OpenAlex

Projections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here, we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal immunoglobulin (IG) domains is necessary and sufficient to create homodimers and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3−/− animals. Our results provide evidence for Kirrel3 homodimerization controlling axonal coalescence.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.697

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.056
GPT teacher head0.237
Teacher spread0.181 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations27
Published2021
Admission routes2
Has abstractyes

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