The epsin protein family: coordinators of endocytosis and signaling

Abstract

The epsins are a conserved family of endocytic adaptors essential for cell viability in yeast and for embryo development in higher eukaryotes. Epsins function as adaptors by recognizing ubiquitinated cargo and as endocytic accessory proteins by contributing to endocytic network stability/regulation and membrane bending. Importantly, epsins play a critical role in signaling by contributing to epidermal growth factor receptor downregulation and the activation of notch and RhoGTPase pathways. In this review, we present an overview of the epsins and emphasize their functional importance as coordinators of endocytosis and signaling.

Figure 1

Schematic representation of a generic mammalian epsin. Cartoon represents typical epsin domain organization, known interaction partners, and signaling links. PIP₂, phosphatidylinositol-4,5-bisphosphate; ENTH, epsin N-terminus homology domain; α₀, helix 0; Ub, ubiquitin; U, ubiquitin-interacting motif; C, clathrin-binding motif; DPW (or DPF), AP2-binding aspartate-proline-tryptophan (or aspartate-proline-phenylalanine) motifs; NPF, asparagine-proline-phenylalanine motif that binds to EH domain-containing proteins, such as Eps15 and intersectin; EH, Eps15 homology domain; AP2, clathrin assembly or adaptor protein 2. Figure is not drawn to scale; not all possible interactions are depicted.

Figure 2

Comparison of domain architecture of epsins from different organisms. Hs, Homo sapiens (NP_037465.2); Sc, S. cerevisiae (NP_010120); Dm, D. melanogaster (AAF05113); Ce, C. elegans (NP_510459); Dd, D. discoideum (XP_635269).