Evidence map›Paper›PMID 41252157›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

The adhesion GPCR ADGRL2 engages Gα13 to enable epidermal differentiation.

Xue Yang, Feng He, Vanessa Lopez-Pajares, Douglas F Porter, Krassimira Garbett, Zurab Siprashvili, Luca Ducoli, Robin M Meyers, David L Reynolds, Duy Lan Huong Bui and 10 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Chemogenetic Activation of GFASEB bioAdvances · 2026
    Article
  2. Article
  3. The adhesion GPCR ADGRL2 engages Gα13 to enable epidermal differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Xue Yang *Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-7142-6741
Feng He *Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Vanessa Lopez-PajaresProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0001-8538-344X
Douglas F PorterProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0001-9491-8258
Krassimira GarbettDepartment of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.ORCID 0000-0003-3969-3919
Zurab SiprashviliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-2814-4220
Luca DucoliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Robin M MeyersProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
David L ReynoldsProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Duy Lan Huong BuiDepartment of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.
Audrey HongProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Duy Thanh NguyenProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Yuqing JingDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-9701-8228
Smarajit MondalProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Lisa KoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-3732-0580
Shiying TaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.
Bharti SingalDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Richard SandoDepartment of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.ORCID 0000-0002-1797-2346
Georgios SkiniotisDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Paul A KhavariProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0003-0098-4989

Funding

Signaling Regulators of Epithelial Homeostasis and NeoplasiaR01AR049737 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 2004 to 2026
$7.1M
NIAMS NIH HHS R01 AR049737
6 · The paper itself

Abstract

Homeostasis relies on signaling networks controlled by cell membrane receptors. Although G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors, their specific roles in the epidermis are not fully understood. Dual CRISPR-Flow and single cell Perturb RNA-sequencing knockout screens of all epidermal GPCRs were thus performed, uncovering an essential requirement for adhesion GPCR ADGRL2 (latrophilin 2) in epidermal differentiation. Among potential downstream guanine nucleotide-binding G proteins, ADGRL2 selectively activated Gα13. Follow-up tissue knockouts verified that Gα13 is also required for epidermal differentiation. A cryoelectron microscopy structure in lipid nanodiscs showed that ADGRL2 engages with Gα13 at multiple interfaces, including via an interaction between ADGRL2 intracellular loop 3 and a Gα13-specific QQQ glutamine triplet sequence in its GTPase domain. In situ gene mutation of this interface sequence impaired epidermal differentiation, highlighting an essential new role for an ADGRL2-Gα13 axis in epidermal differentiation.

Indexed as

Cell DifferentiationEpidermal CellsEpidermisGTP-Binding Protein alpha Subunits, G12-G13Receptors, G-Protein-CoupledReceptors, PeptideAnimalsHumansMiceSignal TransductionGTP-Binding Protein alpha Subunits, G12-G13Receptors, G-Protein-CoupledReceptors, PeptideADGRL2adhesion GPCRepidermal differentiationG proteinsstructual biology

Identifiers

PMID41252157
PMCPMC12663980

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.