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Record W3098571689 · doi:10.1101/354316

Spatial Organization of Rho GTPase signaling by RhoGEF/RhoGAP proteins

2018· preprint· en· W3098571689 on OpenAlexafffund
Paul Markus Müller, Juliane Rademacher, Richard D. Bagshaw, Keziban Merve, Girolamo Giudice, Louise Heinrich, Carolin Barth, Rebecca L. Eccles, Marta Sanchez-Castro, Lennart Brandenburg, Geraldine Mbamalu, Monika Tucholska, Lisa Spatt, Celina Wortmann, Maciej T. Czajkowski, Robert-William Welke, Sunqu Zhang, Vivian Nguyen, Trëndelina Rrustemi, Philipp Trnka, Kiara Freitag, Brett Larsen, Oliver Popp, Philipp Mertins, Chris Bakal, Anne‐Claude Gingras, Olivier Pertz, Frederick P. Roth, Karen Colwill, Tony Pawson, Evangelia Petsalaki, Oliver Rocks

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsCanadian Institute for Advanced ResearchUniversity of TorontoSinai Health SystemLunenfeld-Tanenbaum Research Institute
FundersBiotechnology and Biological Sciences Research CouncilTerry Fox Research InstituteStand Up To CancerKrembil FoundationNational Human Genome Research InstituteCanada Excellence Research Chairs, Government of CanadaOntario GenomicsNational Institutes of HealthCancer Research UKCanadian Institutes of Health ResearchGenome CanadaGovernment of OntarioAvon Foundation for Women
KeywordsCrosstalkCDC42Cell biologyGTPaseBiologyRHOAInteractomeGuanine nucleotide exchange factorRac GTP-Binding ProteinsSignaling proteinsGTPase-activating proteinSignal transductionMorphogenesisRAC1G proteinBiochemistry

Abstract

fetched live from OpenAlex

Abstract Rho GTPases control cell morphogenesis and thus fundamental processes in all eukaryotes. They are regulated by 145 RhoGEF and RhoGAP multi-domain proteins in humans. How the Rho signaling system is organized to generate localized responses in cells and prevent their spreading is not understood. Here, we systematically characterized the substrate specificities, localization and interactome of the RhoGEFs/RhoGAPs and revealed their critical role in contextualizing and spatially delimiting Rho signaling. They localize to multiple compartments providing positional information, are extensively interconnected to jointly coordinate their signaling networks and are widely autoinhibited to remain sensitive to local activation. RhoGAPs exhibit lower substrate specificity than RhoGEFs and may contribute to preserving Rho activity gradients. Our approach led us to uncover a multi-RhoGEF complex downstream of G-protein-coupled receptors controlling a Cdc42/RhoA crosstalk. The spatial organization of Rho signaling thus differs from other small GTPases and expands the repertoire of mechanisms governing localized signaling activity.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

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 head0.008
GPT teacher head0.208
Teacher spread0.200 · 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 source (direct Gemma or distilled Codex), 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

Citations6
Published2018
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicProtein Kinase Regulation and GTPase SignalingFrench-language works237,207