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- W4297146107 abstract "ABSTRACT Many G protein-coupled receptors (GPCRs) reside within cilia of mammalian cells and must undergo regulated exit from cilia for the appropriate transduction of signals such as Hedgehog morphogens. Lysine 63-linked ubiquitin (K63Ub) chains mark GPCRs for regulated removal from cilia, but the molecular basis of K63Ub recognition inside cilia remains elusive. Here we show that the BBSome –the trafficking complex in charge of retrieving GPCRs from cilia– engages the ancestral endosomal sorting factor TOM1L2 (Target of Myb1-Like 2) to recognize UbK63 chains within cilia. TOM1L2 directly binds to UbK63 chains and to the BBSome and targeted disruption of the TOM1L2/BBSome interaction results in the accumulation of TOM1L2, ubiquitin and the GPCRs SSTR3, Smoothened and GPR161 inside cilia. Strikingly, the single cell alga Chlamydomonas also requires its TOM1L2 orthologue to clear ubiquitinated proteins from cilia. We conclude that TOM1L2 broadly enables the retrieval of UbK63-tagged proteins by the ciliary trafficking machinery." @default.
- W4297146107 created "2022-09-27" @default.
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- W4297146107 date "2022-09-25" @default.
- W4297146107 modified "2023-10-15" @default.
- W4297146107 title "The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia" @default.
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- W4297146107 doi "https://doi.org/10.1101/2022.09.23.509287" @default.
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