The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to the base of primary cilia
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Abstract
Primary cilia are antenna-like sensory organelles present on almost all eukaryotic
cells. Their sensory capacity relies on receptors, in particular G-protein-coupled
receptors (GPCRs) which localize to the ciliary membrane. Here we show that
ADGRV1, a member of the GPCR subfamily of adhesion GPCRs, is part of a large
protein network, interacting with numerous proteins of a comprehensive ciliary
proteome. ADGRV1 is localized to the base of prototypic primary cilia in cultured
cells and the modified primary cilia of retinal photoreceptors, where it interacts
with TRiC/CCT chaperonins and the Bardet Biedl syndrome (BBS) chaperonin like proteins. Knockdown of ADGRV1, CCT2 and 3, and BBS6 result in common
ciliogenesis phenotypes, namely reduced ciliated cells combined with shorter
primary cilia. In addition, the localization of ADGRV1 to primary cilia depends on
the activity of a co-complex of TRiC/CCT chaperonins and the BBS chaperonin like proteins. In the absence of components of the TRiC/CCT-BBS chaperonin
co-complex, ADGRV1 is depleted from the base of the primary cilium and
degraded via the proteasome. Defects in the TRiC/CCT-BBS chaperonin may
lead to an overload of proteasomal degradation processes and imbalanced
proteostasis. Dysfunction or absence of ADGRV1 from primary cilia may
underly the pathophysiology of human Usher syndrome type 2 and epilepsy
caused by mutations in ADGRV1.
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Frontiers in cell and developmental biology, 13, Frontiers Media, Lausanne, 2025, https://doi.org/10.3389/fcell.2025.1520723