title: α-Arrestins participate in cargo selection for both clathrin-independent and clathrin-mediated endocytosis.
abstract: Clathrin-mediated endocytosis (CME) is a well-studied mechanism to internalize plasma membrane proteins; however, to endocytose such cargo, most eukaryotic cells also use alternative clathrin-independent endocytic (CIE) pathways, which are less well characterized. The budding yeast Saccharomyces cerevisiae, a widely used model for studying CME, was recently shown to have a CIE pathway that requires the GTPase Rho1, the formin Bni1, and their regulators. Nevertheless, in both yeast and mammalian cells, the mechanisms underlying cargo selection in CME and CIE are only beginning to be understood. For CME in yeast, particular α-arrestins contribute to recognition of specific cargos and promote their ubiquitylation by recruiting the E3 ubiquitin protein ligase Rsp5. Here, we show that the same α-arrestin-cargo pairs promote internalization through the CIE pathway by interacting with CIE components. Notably, neither expression of Rsp5 nor its binding to α-arrestins is required for CIE. Thus, α-arrestins are important for cargo selection in both the CME and CIE pathways, but function by distinct mechanisms in each pathway.
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA odonne15@duq.edu dprosser@jhu.edu.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Prosser
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pannunzio
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
authors.affiliation: Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Wendland
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282, USA odonne15@duq.edu dprosser@jhu.edu.
authors.forename: Allyson F
authors.initials: AF
authors.lastname: O'Donnell
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D001692:Biological Transport / Q000235:genetics*; D002462:Cell Membrane; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D019390:Arrestins; D002966:Clathrin; D008565:Membrane Proteins; D044767:Ubiquitin-Protein Ligases
keywords: Internalization; Plasma membrane; Protein trafficking; Ubiquitin ligase; Yeast