A single domain intrabody biases the follicle-stimulating hormone receptor subcellular trafficking
Abstract
Variable fragments from camelid heavy-chain only antibodies (VHH) can stabilize active conformations of G protein-coupled receptors (GPCRs), enabling 3D structural characterization and supporting detailed structure–activity studies by linking receptor conformational states to downstream signaling. When expressed intracellularly, these VHHs have recently proven useful for tracking active GPCRs across subcellular compartments. Here, we report the isolation and characterization of iPRC2, an intra-VHH that selectively recognizes intracellular loops of the human follicle-stimulating hormone receptor (hFSHR). Expression of iPRC2 in hFSHR-expressing cells reduces FSH-induced cAMP accumulation, while requiring G α s for optimal receptor interaction. Importantly, iPRC2 promotes hFSHR accumulation in early endosomes and limits its recycling to the cell surface. Hence, unlike previously described intra-VHHs that recognize active GPCR intracellular location, iPRC2 induces per se a location bias. By reshaping hFSHR trafficking, iPRC2 provides a unique live-cell tool to manipulate receptor localization and investigate how compartmentalized GPCR trafficking influences signaling outputs.
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BibTeX
@article{raynaud2026single,
title = {{A single domain intrabody biases the follicle-stimulating hormone receptor subcellular trafficking}},
author = {Pauline Raynaud and Juliette Gourdon and Vinesh Jugnarain and Frédéric Jean-Alphonse and Lucille Berthet and Violaine Moreau and Chloé Weckel and Océane Vaugrente and Camille Gauthier and Amandine Vallet and Romain Yvinec and Priyanka Anujan and Delphine Naquin and Thomas Boulo and Julien Pichon and Christophe Gauthier and Danièle Klett and Yves Combarnous and Nathalie Sibille and Aylin Hanyaloglu and Eric Reiter and Gilles Bruneau and Pascale Crépieux},
journal = {Communications Biology},
year = {2026},
month = sep,
doi = {10.1038/s42003-026-11015-z},
url = {https://hal.inrae.fr/hal-05841733v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A single domain intrabody biases the follicle-stimulating hormone receptor subcellular trafficking
AU - Pauline Raynaud
AU - Juliette Gourdon
AU - Vinesh Jugnarain
AU - Frédéric Jean-Alphonse
AU - Lucille Berthet
AU - Violaine Moreau
AU - Chloé Weckel
AU - Océane Vaugrente
AU - Camille Gauthier
AU - Amandine Vallet
AU - Romain Yvinec
AU - Priyanka Anujan
AU - Delphine Naquin
AU - Thomas Boulo
AU - Julien Pichon
AU - Christophe Gauthier
AU - Danièle Klett
AU - Yves Combarnous
AU - Nathalie Sibille
AU - Aylin Hanyaloglu
AU - Eric Reiter
AU - Gilles Bruneau
AU - Pascale Crépieux
PY - 2026
DA - 2026/09/23
JO - Communications Biology
DO - 10.1038/s42003-026-11015-z
UR - https://hal.inrae.fr/hal-05841733v1
AB - Variable fragments from camelid heavy-chain only antibodies (VHH) can stabilize active conformations of G protein-coupled receptors (GPCRs), enabling 3D structural characterization and supporting detailed structure–activity studies by linking receptor conformational states to downstream signaling. When expressed intracellularly, these VHHs have recently proven useful for tracking active GPCRs across subcellular compartments. Here, we report the isolation and characterization of iPRC2, an intra-VHH that selectively recognizes intracellular loops of the human follicle-stimulating hormone receptor (hFSHR). Expression of iPRC2 in hFSHR-expressing cells reduces FSH-induced cAMP accumulation, while requiring G α s for optimal receptor interaction. Importantly, iPRC2 promotes hFSHR accumulation in early endosomes and limits its recycling to the cell surface. Hence, unlike previously described intra-VHHs that recognize active GPCR intracellular location, iPRC2 induces per se a location bias. By reshaping hFSHR trafficking, iPRC2 provides a unique live-cell tool to manipulate receptor localization and investigate how compartmentalized GPCR trafficking influences signaling outputs.
SN - 2399-3642
ER -