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Phenotypes

Mouse phenotype:

increased heart weight

Subcellular localization

cilia, Nucleoplasm

Functional category

• Motors (dynein/kinesin)
• Trafficking (BBSome
• small GTPases
• vesicular transport
• ATPases)
• Signaling (Hedgehog
• GPCRs
• ion channels)

Function

We demonstrate that β-arrestins mediate the activity-dependent interaction of Smo and the kinesin motor protein Kif3A. This multimeric complex localized to primary cilia and was disrupted in cells transfected with β-arrestin siRNA. β-arrestin 1 or β-arrestin 2 depletion prevented localization of Smo to primary cilia and Smo-dependent activation of Gli. These results support roles for β-arrestins in mediating the intracellular transport of a 7TMR to its obligate subcellular location for signaling(18497258). Plasma membrane GPCRs undergo phosphorylation by GPCR kinases (GRKs) and subsequent binding of β-arrestins [β-arrestin1 (ARRB1) and β-arrestin2 (ARRB2)], which is crucial for clathrin-mediated endocytosis. We here confirmed that GPR161 and β-arrestin are accumulated within cilia in the absence of IFT27 or the BBSome, and that ARRB1 and ARRB2 double-knockout impairs GPR161 export. Notably, we found that activation-mimetic β-arrestin mutants can interact with both the BBSome and ciliary GPCRs, and cause constitutive export of GPR161. Moreover, we demonstrated that GRK2 plays a crucial role in GPR161 export. We here propose that phosphorylated GPR161 recruits β-arrestins, converting them into their activated conformation. Activated β-arrestins then interact with the BBSome, which connects them to the IFT machinery to facilitate GPR161 export(40384633).