Direct tensile force activates Adgrl3 in a tethered agonist-dependent manner

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Jesper Holmkvist, Luis E. Hamel Ascanio, Younes Farhangi Barooji, Yin Kwan Chung, Rajesh Regmi, Phillip C. Vejre, Júlia Rosell-Teixidó, Karen L. Martinez, METTE MARIE ROSENKILDE, Poul Martin Bendix, Jonathan A. Javitch, Signe Mathiasen
DOI: 10.64898/2026.02.27.706744
Cited by: 0
References: 27

Abstract

Adhesion G protein-coupled receptors are proposed to function as mechanosensors, yet whether controlled mechanical force can directly activate receptor signaling in living cells remains unclear. Using optical tweezers, we demonstrate that direct tensile force applied to the N-terminus of the adhesion GPCR Adgrl3 is sufficient to induce G protein recruitment in living cells. Activation is direction-specific, requires a functional tethered agonist, and aligns with coexisting force-driven GAIN-domain conformational changes and dissociation.

Fields of Study & Subjects

Receptor Mechanisms and Signaling Protein Kinase Regulation and GTPase Signaling Cellular Mechanics and Interactions

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publication date
1 March 2026
Language
EN
Document type
Preprint