Related Experiment Video
Updated: May 23, 2025

Tension Gauge Tether Probes for Quantifying Growth Factor Mediated Integrin Mechanics and Adhesion
Published on: February 11, 2022
The Adhesion GPCR ADGRL2 engages Gα13 to Enable Epidermal Differentiation
Xue Yang1,2,3, Feng He4,3, Douglas F Porter1
1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
None:
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-seq 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. Perturb-seq of epidermal G proteins and follow-up tissue knockouts verified that Gα13 is also required for epidermal differentiation. A cryo-electron microscopy (cryo-EM) structure in lipid nanodiscs showed that ADGRL2 engages with Gα13 at multiple interfaces, including via a novel interaction between ADGRL2 intracellular loop 3 (ICL3) 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.
Related Concept Videos
Activation and Inactivation of G Proteins
TGF - β Signaling Pathway
Intracellular Signaling Affects Focal Adhesions
Some...
Renewal of Skin Epidermal Stem Cells
GPCRs Regulate Adenylyl Cylase Activity
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...

