Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • R. Claudio AguilarEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101568


Historical Background

In 1998 the De Camilli Lab (Yale University) isolated a novel protein able to bind the endocytic protein eps15 from rat brain extracts and accordingly named it as Eps15 interacting protein 1, Epsin-1 or just Epn1 (Fig. 1 and Chen et al. 1998). Conservation of Epn1 was evident as sequence comparison revealed homology to the mitotic phosphoprotein-90 from Xenopus laevis and to the Ent1 and Ent2 yeast proteins. The Epn1 paralog, Epn2, was also discovered by the De Camilli Lab the following year (Rosenthal et al. 1999) which along with Epn1 was found localized at the plasma membrane and to participate in clathrin-mediated endocytosis (Sen et al. 2012; Wendland 2002). While these Epn paralogs showed widespread expression with substantial enrichment in the brain, a later described third paralog named epsin-3 was found to be virtually restricted to keratinocytes, gastric parietal cells, and several carcinomas (Sen et al. 2012).
This is a preview of subscription content, log in to check access.



I thank the members of the Aguilar Lab for input. I apologize to all authors whose original contributions we could not cite due to space limitations. For more complete listings, please refer to the cited reviews and references therein. The Aguilar Lab is supported by grants from the National Science Foundation MCB-1021377 and by the Center for Science of Information (CSoI), an NSF Science and Technology Center, under grant agreement CCF-0939370.


  1. Aguilar RC, Longhi SA, Shaw JD, Yeh LY, Kim S, Schon A, et al. Epsin N-terminal homology domains perform an essential function regulating Cdc42 through binding Cdc42 GTPase-activating proteins. Proc Natl Acad Sci USA. 2006;103(11):4116–21.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Brady RJ, Damer CK, Heuser JE, O’Halloran TJ. Regulation of Hip1r by epsin controls the temporal and spatial coupling of actin filaments to clathrin-coated pits. J Cell Sci. 1 Nov 2010;123(Pt 21):3652–3661.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Chang B, Tessneer KL, McManus J, Liu X, Hahn S, Pasula S, Wu H, Song H, Chen Y, Cai X, Dong Y, Brophy ML, Rahman R, Ma JX, Xia L, Chen H. Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development. Nat Commun. 16 Mar 2015;6:6380. doi: 10.1038/ncomms7380.Google Scholar
  4. Chen C, Zhuang X. Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus. Proc Natl Acad Sci U S A. 2008;105(33):11790–5.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature. 1998;394(6695):793–7.CrossRefPubMedGoogle Scholar
  6. Chen B, Dores MR, Grimsey N, Canto I, Barker BL, Trejo J. AP-2 and epsin-1 mediate protease-activated receptor-1 internalization via phosphorylation- and ubiquitination-dependent sorting signals. J Biol Chem. 2011;286(47):40760–70.Google Scholar
  7. Coon BG, Burgner J, Camonis JH, Aguilar RC. The epsin family of endocytic adaptors promotes fibrosarcoma migration and invasion. J Biol Chem. 2010;285(43):33073–81.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Csikós G, Lippai M, Lukácsovich T, Juhász G, Henn L, Erdélyi M, et al. A novel role for the Drosophila epsin (lqf): involvement in autophagy. Autophagy. 2009;5(5):636–48.CrossRefPubMedGoogle Scholar
  9. Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, et al. Curvature of clathrin-coated pits driven by epsin. Nature. 2002;419(6905):361–6.CrossRefPubMedGoogle Scholar
  10. Goh LK, Huang F, Kim W, Gygi S, Sorkin A. Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptor. J Cell Biol. 2010;189(5):871–83.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Henry AG, Hislop JN, Grove J, Thorn K, Marsh M, von Zastrow M. Regulation of endocytic clathrin dynamics by cargo ubiquitination. Dev Cell. 11 Sep 2012;23(3):519–532.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Kang YL, Yochem J, Bell L, Sorensen EB, Chen L, Conner SD. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1. Mol Biol Cell. Feb 2013;24(3):308–318.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Liu X, Pasula S, Song H, Tessneer KL, Dong Y, Hahn S, Yago T, Brophy ML, Chang B, Cai X, Wu H, McManus J, Ichise H, Georgescu C, Wren JD, Griffin C, Xia L, Srinivasan RS, Chen H. Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function. Sci Signal. 14 Oct 2014;7(347):ra97.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Meloty-Kapella L, Shergill B, Kuon J, Botvinick E, Weinmaster G. Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin. Dev Cell. 12 Jan 2012;22(6):1299–1312.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Messa M, Fernández-Busnadiego R, Sun EW, Chen H, Czapla H, Wrasman K, Wu Y, Ko G, Ross T, Wendland B, De Camilli P. Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits. Elife. 13 Aug 2014;3:e03311. 10.7554/eLife.03311.Google Scholar
  16. Mettlen M, Stoeber M, Loerke D, Antonescu CN, Danuser G, Schmid SL. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009;20(14):3251–60.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Mukherjee D, Coon BG, Edwards DF, Hanna CB, Longhi SA, McCaffery JM, et al. The yeast endocytic protein Epsin 2 functions in a cell-division signaling pathway. J Cell Sci. 2009;122(14):2453–63.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Pasula S, Cai X, Dong Y, Messa M, McManus J, Chang B, Liu X, Zhu H, Mansat RS, Yoon SJ, Hahn S, Keeling J, Saunders D, Ko G, Knight J, Newton G, Luscinskas F, Sun X, Towner R, Lupu F, Xia L, Cremona O, De Camilli P, Min W, Chen H. Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling. J Clin Invest. Dec 2012;122(12):4424–4438.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Rosenthal JA, Chen H, Slepnev VI, Pellegrini L, Salcini AE, Di Fiore PP, et al. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. J Biol Chem. 1999;274(48):33959–65.CrossRefPubMedGoogle Scholar
  20. Sen A, Madhivanan K, Mukherjee D, Aguilar RC. The epsin protein family: coordinators of endocytosis and signaling. Biomol Concepts. Apr 2012;3(2):117–126.Google Scholar
  21. Sorkina T, Miranda M, Dionne KR, Hoover BR, Zahniser NR, Sorkin A. RNA interference screen reveals an essential role of Nedd4-2 in dopamine transporter ubiquitination and endocytosis. J Neurosci. 2006;26(31):8195–205.CrossRefPubMedGoogle Scholar
  22. Sorrentino V, Nelson JK, Maspero E, Marques AR, Scheer L, Polo S, Zelcer N. The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation. J Lipid Res. Aug 2013;54(8):2174–2184.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Sugiyama S, Kishida S, Chayama K, Koyama S, Kikuchi A. Ubiquitin-interacting motifs of Epsin are involved in the regulation of insulin-dependent endocytosis. J Biochem. 2005;137(3):355–64.CrossRefPubMedGoogle Scholar
  24. Szymanska M, Fosdahl AM, Raiborg C, Dietrich M, Liestøl K, Stang E, Bertelsen V. Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3. Biochim Biophys Acta. Jun 2016;1863(6 Pt A):1179–1188.CrossRefGoogle Scholar
  25. Wang H, Traub LM, Weixel KM, Hawryluk MJ, Shah N, Edinger RS, et al. Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin. J Biol Chem. 2006;281(20):14129–35.CrossRefPubMedGoogle Scholar
  26. Wendland B. Epsins: adaptors in endocytosis? Nat Rev Mol Cell Biol. 2002;3(12):971–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Biological SciencesPurdue UniversityWest LafayetteUSA