Regulation of Endocytic Clathrin Dynamics by Cargo Ubiquitination

Henry, Anastasia G.; Hislop, James N.; Grove, Joe; Thorn, Kurt S.; Marsh, Mark; Zastrow, Mark von

doi:10.1016/j.devcel.2012.08.003

Cited by 95 publications

(104 citation statements)

References 70 publications

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“…In particular, recent work suggests that ubiquitin can directly influence the maturation of a coated pit by acting as a signaling molecule in a dose-dependent fashion. Interestingly, the plasma membrane distribution of the mu opioid receptors, which undergo ubiquitin modification upon agonist stimulation, does not overlap uniformly with clathrin when activated, supporting the idea that multiple, distinct populations of clathrin-coated pits exist (39). These findings also raise the possibility that ubiquitin-mediated signaling during pit maturation is coupled to ESCRT-0 recruitment.…”

Section: The Fei Adaptor Complex Regulates Protein Sorting In the Endsupporting

confidence: 58%

Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Mayers¹,

Wang²,

Pramanik³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Endocytic protein trafficking is directed by sorting signals on cargo molecules that are recognized by cytosolic adaptor proteins. However, the steps necessary to segregate the variety of cargoes during endocytosis remain poorly defined. Using Caenorhabditis elegans, we demonstrate that multiple plasma membrane endocytic adaptors function redundantly to regulate clathrin-mediated endocytosis and to recruit components of the endosomal sorting complex required for transport (ESCRT) machinery to the cell surface to direct the sorting of ubiquitin-modified substrates. Moreover, our data suggest that preassembly of cargoes with the ESCRT-0 complex at the plasma membrane enhances the efficiency of downstream sorting events in the endolysosomal system. In the absence of a heterooligomeric adaptor complex composed of FCHO, Eps15, and intersectin, ESCRT-0 accumulation at the cell surface is diminished, and the degradation of a ubiquitin-modified cargo slows significantly without affecting the rate of its clathrin-mediated internalization. Consistent with a role for the ESCRT machinery during cargo endocytosis, we further show that the ESCRT-0 complex accumulates at a subset of clathrin-coated pits on the surface of human cells. Our findings suggest a unique mechanism by which ubiquitin-modified cargoes are sequestered into the endolysosomal pathway.clathrin | multivesicular endosome

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Section: The Fei Adaptor Complex Regulates Protein Sorting In the Endsupporting

confidence: 58%

Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Mayers¹,

Wang²,

Pramanik³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…One possibility is that Ub cargoes are not simply passive passengers but that their Ub moiety helps properly assemble and orchestrate the clathrin-coated vesicle formation through interaction with UBDs of the associated machinery. This possibility is supported by experiments showing that the presence of Ub on cargo affects the dynamics of clathrin-coated vesicle (CCV) assembly (Henry et al 2012). This view is also consistent with experiments on the endocytic Ub-sorting ESCRT apparatus that relies on the presence of ubiquitinated cargo to productively assemble on the surface of endosomes (MacDonald et al 2012a).…”

Section: How Ubiquitin Mediates Internalization From the Plasma Membranesupporting

confidence: 48%

Ubiquitin-Dependent Sorting in Endocytosis

Piper

Đikić

Lukacs

2014

Cold Spring Harbor Perspectives in Biology

194

176

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When ubiquitin (Ub) is attached to membrane proteins on the plasma membrane, it directs them through a series of sorting steps that culminate in their delivery to the lumen of the lysosome where they undergo complete proteolysis. Ubiquitin is recognized by a series of complexes that operate at a number of vesicle transport steps. Ubiquitin serves as a sorting signal for internalization at the plasma membrane and is the major signal for incorporation into intraluminal vesicles of multivesicular late endosomes. The sorting machineries that catalyze these steps can bind Ub via a variety of Ub-binding domains. At the same time, many of these complexes are themselves ubiquitinated, thus providing a plethora of potential mechanisms to regulate their activity. Here we provide an overview of how membrane proteins are selected for ubiquitination and deubiquitination within the endocytic pathway and how that ubiquitin signal is interpreted by endocytic sorting machineries. HOW PROTEINS ARE SELECTED FOR UBIQUITINATIONU biquitin (Ub) is covalently attached to substrate proteins by the concerted action of E2-conjugating enzymes and E3 ligases (Varshavsky 2012). Most of the specificity and regulation of ubiquitination is at the level of the E3 ligases, which vastly outnumber the E2-conjugating enzymes. Ubiquitination results from the transfer of Ub, held either by the E2 or in some cases by the E3 as a high-energy thioester bond, onto a substrate protein, typically on the terminal amide of a substrate acceptor lysine side chain. Owing to the intense interest in the ubiquitination system, many of the simple rules and distinctions concerning different types of ligases, their specificity for forming particular polyUb chains, and even the kinds of residues in substrate proteins that can be ubiquitin modified, have been blurred with the discovery of mixed poly-Ub chains, new enzymatic mechanisms for Ub transfer, and ubiquitination of nonlysine residues (Kulathu and Komander 2012;Wenzel and Klevit 2012;McDowell and Philpott 2013). Nonetheless, in basic terms, Ub ligases function as platforms that coordinate substrate recognition with Ub transfer as well as configuring poly-Ub chain topology by the E2-conjugating enzyme. Substrates can be bound directly by the E3 ligase or by adaptor proteins that in turn bind to ligases, and selecEditors:

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“…Genetic studies in yeast have revealed roles for epsins in recognition of ubiquitinated cargo molecules (58), as a scaffold for assembly and organization of components of the early endocytic machinery (59) and as a platform for actin assembly (60). Studies in mammalian cells have suggested a role for epsin as an adaptor for ubiquitinated cargo (61,62) and shown that it is recruited early to CCPs along with other adaptor and scaffolding molecules (63), where it potentially regulates early stages of CCP maturation (62). Together, these in vivo findings are more consistent with a role for epsin at earlier stages of CME.…”

Section: Discussionmentioning

confidence: 99%

Dual Role of BAR Domain-containing Proteins in Regulating Vesicle Release Catalyzed by the GTPase, Dynamin-2

Neumann

Schmid

2013

Journal of Biological Chemistry

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Background: Membrane curvature generation is essential for dynamin-2-catalyzed membrane fission and vesicle release. Results: Dynamin-2 binding partners with curvature generating activity differentially regulate the assembly, GTPase, and fission activities of dynamin-2. Conclusion: Dynamin-2 partners display complex patterns of regulation. Significance: The distinct functional interactions between dynamin-2 and its binding partners position them to contribute to the spatio-temporal regulation of clathrin-mediated endocytosis.

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Regulation of Endocytic Clathrin Dynamics by Cargo Ubiquitination

Cited by 95 publications

References 70 publications

Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Ubiquitin-Dependent Sorting in Endocytosis

Dual Role of BAR Domain-containing Proteins in Regulating Vesicle Release Catalyzed by the GTPase, Dynamin-2

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