Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein

Matthew J. Hawryluk, Peter A. Keyel, Sanjay K. Mishra, Simon C. Watkins, John E. Heuser, Linton M. Traub

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


Epsin 1 engages several core components of the endocytic clathrin coat, yet the precise mode of operation of the protein remains controversial. The occurrence of tandem ubiquitin-interacting motifs (UlMs) suggests that epsin could recognize a ubiquitin internalization tag, but the association of epsin wilth clathrin-coat components or monoubiquitin is reported to be mutually exclusive. Here, we show that endogenous epsin 1 is clearly an integral component of clathrin coats forming at the cell surface and is essentially absent from caveolin-1-containing structures under normal conditions. The UIM region of epsin 1 associates directly with poly-ubiquitin chains but has extremely poor affinity for monoubiquitin. Polyubiquitin binding is retained when epsin synchronously associates with phosphoinositides, the AP-2 adaptor complex and clathrin. The enrichment of epsin within clathrin-coated vesicles purified from different tissue sources varies and correlates with sorting of multiubiquitinated cargo, and in cultured cells, polyubiquitin, rather than non-conjugable monoubiquitin, promotes rapid internalization. As epsin interacts with eps15, which also contains a UIM region that binds to polyubiquitin, epsm and eps15 appear to be central components of the vertebrate poly/muftiubiquitin-sorting endocytic clathrin machinery.

Original languageEnglish
Pages (from-to)262-281
Number of pages20
Issue number3
StatePublished - Mar 2006


  • Cargo
  • Clathrin
  • Endocytosis
  • Eps15
  • Epsin
  • Ubiquitin


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