Evidence map›Paper›PMID 40512625›Full record

ArticleCell reports2025

Aberrant phase separation of two PKA RIβ neurological disorder mutants leads to mechanistically distinct signaling deficits.

Emily H Pool, Alexander Glebov-McCloud, Ha Neul Lee, Julia C Hardy, Valeria Pane, Friedrich W Herberg, Susan S Taylor, Sohum Mehta, Stefan Strack, Jin Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Emily H PoolDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Alexander Glebov-McCloudDepartment of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA.
Ha Neul LeeDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Julia C HardyDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Valeria PaneDepartment of Biochemistry, University of Kassel, 34132 Kassel, Germany.
Friedrich W HerbergDepartment of Biochemistry, University of Kassel, 34132 Kassel, Germany.
Susan S TaylorDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Sohum MehtaDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Stefan StrackDepartment of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242, USA. Electronic address: stefan-strack@uiowa.edu.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jzhang32@health.ucsd.edu.

Funding

Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Lessons Learned from PKA: Assembly of Dynamic Macromolecular SwitchesR35GM130389 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUSAN S. TAYLOR · 2019 to 2026
$5.7M
Interdisciplinary Training Program in Pain ResearchT32NS045549 · NINDS · UNIVERSITY OF IOWA · PI KATHLEEN A SLUKA, Yuriy M Usachev · 2004 to 2026
$3.7M
Predoctoral Training in the Pharmacological SciencesT32GM067795 · NIGMS · UNIVERSITY OF IOWA · PI STRACK, STEFAN · 2004 to 2021
$3.4M
Predoctoral Training in the Pharmacological SciencesT32GM144636 · NIGMS · UNIVERSITY OF IOWA · PI David L. Roman, STEFAN STRACK · 2022 to 2026
$1.9M
Interplay between tau and PKA condensates in ADRDR21AG080472 · NIA · UNIVERSITY OF IOWA · PI STRACK, STEFAN, TAYLOR, SUSAN S. · 2023 to 2024
$559k
NCI NIH HHS R35 CA197622NIA NIH HHS R21 AG080472NIDDK NIH HHS R01 DK073368NIGMS NIH HHS R35 GM130389NIGMS NIH HHS T32 GM008326NIGMS NIH HHS T32 GM067795NIGMS NIH HHS T32 GM144636NINDS NIH HHS T32 NS045549
6 · The paper itself

Abstract

Spatiotemporal regulation of key-node signaling molecules, such as 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), is critical for normal cell physiology and susceptible to dysregulation in disease. Liquid-liquid phase separation (LLPS) is broadly recognized as a fundamental component of signal regulation, yet the connections between physiological and disease-linked biomolecular condensates are not well understood. Here, we show that an understudied, brain-specific PKA regulatory subunit, RIβ, forms biomolecular condensates with distinct features from the ubiquitous isoform, RIα. We demonstrate that two RIβ mutants linked to neurodegenerative (L50R) or neurodevelopmental (R335W) pathologies produce aberrant condensates that trap the PKA catalytic subunit within a gel-like matrix or cAMP-insensitive holoenzyme complex, respectively. RIβ

Indexed as

Cyclic AMP-Dependent Protein Kinase RIIbeta SubunitMutationNervous System DiseasesSignal TransductionAnimalsCyclic AMPCyclic AMP-Dependent Protein KinasesHumansMicePhase SeparationCyclic AMPCyclic AMP-Dependent Protein Kinase RIIbeta SubunitCyclic AMP-Dependent Protein Kinasesbiomolecular condensatescAMPCP: Molecular biologyCP: Neuroscienceneurodegenerationneurodevelopmentprotein kinasesignaling compartmentation

Identifiers

PMID40512625
PMCPMC12369641

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.