title: Evolutionary Changes on the Way to Clathrin-Mediated Endocytosis in Animals.
abstract: Endocytic pathways constitute an evolutionarily ancient system that significantly contributed to the eukaryotic cell architecture and to the diversity of cell type-specific functions and signaling cascades, in particular of metazoans. Here we used comparative proteomic studies to analyze the universal internalization route in eukaryotes, clathrin-mediated endocytosis (CME), to address the issues of how this system evolved and what are its specific features. Among 35 proteins crucially required for animal CME, we identified a subset of 22 proteins common to major eukaryotic branches and 13 gradually acquired during evolution. Based on exploration of structure-function relationship between conserved homologs in sister, distantly related and early diverged branches, we identified novel features acquired during evolution of endocytic proteins on the way to animals: Elaborated way of cargo recruitment by multiple sorting proteins, structural changes in the core endocytic complex AP2, the emergence of the Fer/Cip4 homology domain-only protein/epidermal growth factor receptor substrate 15/intersectin functional complex as an additional interaction hub and activator of AP2, as well as changes in late endocytic stages due to recruitment of dynamin/sorting nexin 9 complex and involvement of the actin polymerization machinery. The evolutionary reconstruction showed the basis of the CME process and its subsequent step-by-step development. Documented changes imply more precise regulation of the pathway, as well as CME specialization for the uptake of specific cargoes and cell type-specific functions.
authors.affiliation: Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, Kyiv, Ukraine m.v.dergai@imbg.org.ua.
authors.forename: Mykola
authors.initials: M
authors.lastname: Dergai
authors.affiliation: Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, NASU, Kyiv, Ukraine.
authors.forename: Anton
authors.initials: A
authors.lastname: Iershov
authors.affiliation: Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, Kyiv, Ukraine.
authors.forename: Olga
authors.initials: O
authors.lastname: Novokhatska
authors.affiliation: Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, Kyiv, Ukraine.
authors.forename: Serhii
authors.initials: S
authors.lastname: Pankivskyi
authors.affiliation: Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, Kyiv, Ukraine.
authors.forename: Alla
authors.initials: A
authors.lastname: Rynditch
mesh_terms: D002966:Clathrin / Q000235:genetics*; D004705:Endocytosis / Q000235:genetics*; D056890:Eukaryota / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D040901:Proteomics; D013329:Structure-Activity Relationship
chemical_list: D002966:Clathrin; D011506:Proteins
keywords: clathrin-associated sorting proteins; dynamin/SNX9 complex; endocytic protein interaction network; evolution of endocytic system; regulation of AP2 conformational switch; scaffolding FCHO/Eps15/ITSN complex