Regulation of endocytic clathrin dynamics by cargo ubiquitination

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)
11 Downloads (Pure)


Some endocytic cargoes control clathrin-coated pit (CCP) maturation, but it is not known how such regulation is communicated. We found that R-opioid neuropeptide receptors signal to their enclosing CCPs by ubiquitination. Nonubiquitinated receptors delay CCPs at an intermediate stage of maturation, after clathrin lattice assembly is complete but before membrane scission. Receptor ubiquitination relieves this inhibition, effectively triggering CCP scission and producing a receptor-containing endocytic vesicle. The ubiquitin modification that conveys this endocytosis-promoting signal is added to the receptor's first cytoplasmic loop, catalyzed by the Smurf2 ubiquitin ligase, and coordinated with activation-dependent receptor phosphorylation and clustering through Smurf2 recruitment by the endocytic adaptor beta-arrestin. Epsin1 detects the signal at the CCP and is required for ubiquitin-promoted scission. This cargo-to-coat communication system mediates a biochemical checkpoint that ensures appropriate receptor ubiquitination for later trafficking, and it controls specific receptor loading into CCPs by sensing when a sufficient quorum is reached.

Original languageEnglish
Pages (from-to)519-532
Number of pages14
JournalDevelopmental Cell
Issue number3
Publication statusPublished - 11 Sept 2012


  • coated pits
  • plasma-membrane
  • internalization
  • beta-arrestins
  • opioid receptors
  • mediated endocytosis
  • membrane curvature
  • BETA(2)-adrenergic receptor
  • protein-coupled receptors
  • agonist


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