The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia
Swapnil Rohidas Shinde,David U. Mick,Erika Aoki,Rachel B. Rodrigues,Steven P. Gygi,Maxence V. Nachury +5 more
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TLDR
It is shown 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, which broadly enables the retrieval of UbK 63-tagged proteins by the ciliary trafficking machinery.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.read more
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Cargo adapters expand the transport range of intraflagellar transport.
TL;DR: The authors in this paper summarized the individual and shared features of the known cargo adapters and discussed their possible role in regulating the transport capacity of the intraflagellar transport (IFT) pathway.
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Primary cilia as dynamic and diverse signalling hubs in development and disease
TL;DR: In this paper , the structural and functional diversity of primary cilia, their dynamic regulation in different cellular and developmental contexts and their disruption in disease are examined, and a review of the structural diversity of cilia is presented.
Journal ArticleDOI
A targeted multi-proteomics approach generates a blueprint of the ciliary ubiquitinome
Mariam G Aslanyan,Cenna Doornbos,Gaurav D. Diwan,Zeinab Anvarian,Tina Beyer,Katrin Junger,Sylvia E. C. van Beersum,Robert B. Russell,Marius Ueffing,Alexander Ludwig,Karsten Boldt,Lotte B. Pedersen,Ronald Roepman +12 more
TL;DR: In this paper , the authors take an unbiased approach to generate a comprehensive blueprint of the ciliary ubiquitinome by deploying a multi-proteomics approach using both ciliary-targeted UBP affinity proteomics, as well as UBP-binding domain-based proximity labeling in two different mammalian cell lines.
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GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade
Madison F. Walker,Jingyi Zhang,P. Ku,Ju-Fen Zhu,Yu-Chen Yen,Alyssa B. Long,Mattie J. Casey,Abhishek Poddar,Isaac B. Nelson,Corvin D. Arveseth,Falko Nagel,Ryan Clough,Sarah LaPotin,Kristen M. Kwan,Rodney A. Stewart,John J.G. Tesmer,Tamara Caspary,Radhika Subramanian,Xuecai Ge,Benjamin R. Myers +19 more
TL;DR: In this paper , the authors show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the primary cilium, and that upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction.
Journal ArticleDOI
Organization, functions, and mechanisms of the BBSome in development, ciliopathies, and beyond
Huijie Zhao,Jun Zhou +1 more
TL;DR: In this article , the structural assembly, transport regulation, and molecular functions of the BBSome complex are reviewed, emphasizing its roles in cilium-related processes and perspectives on the pathological role of the complex in ciliopathies as well as how these can be exploited for therapeutic benefit.
References
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A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis
Maxence V. Nachury,Alexander V. Loktev,Qihong Zhang,Christopher J. Westlake,Johan Peränen,Andreas Merdes,Diane C. Slusarski,Richard H. Scheller,J. Fernando Bazan,Val C. Sheffield,Peter K. Jackson +10 more
TL;DR: The data reveal that BBS may be caused by defects in vesicular transport to the cilium, and a complex composed of seven highly conserved BBS proteins is identified, the BBSome, which localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cILium.
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Statistical analysis of membrane proteome expression changes in Saccharomyces cerevisiae.
Boris Zybailov,Amber L. Mosley,Mihaela E. Sardiu,Michael K. Coleman,Laurence Florens,Michael P. Washburn +5 more
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The Conserved Bardet-Biedl Syndrome Proteins Assemble a Coat that Traffics Membrane Proteins to Cilia
Hua Jin,Susan Roehl White,Toshinobu Shida,Stefan Schulz,Mike Aguiar,Steven P. Gygi,J. Fernando Bazan,Maxence V. Nachury +7 more
TL;DR: The BBSome constitutes a coat complex that sorts membrane proteins to primary cilia and it is proposed that trafficking of BBSome cargoes to cilia entails the coupling ofBBSome coat polymerization to the recognition of sorting signals by the BBSome.