Epsin N-terminal homology domains perform an essential function regulating Cdc42 through binding Cdc42 GTPase-activating proteins

• Autores: Aguilar, R.C.; Longhi, S.A.; Shaw, J.D.; Yeh, L.-Y.; Kim, S.; Schön, A.; Freire, E.; Hsu, A.; McCormick, W.K.; Watson, H.A.; Wendland, B.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Proc. Natl. Acad. Sci. U. S. A. 2006;103(11):4116-4121
• Materia: Actin; Endocytosis; Polarity; clathrin; epsin; guanosine triphosphatase activating protein; phosphatidylinositide; protein Cdc42; scaffold protein; amino terminal sequence; article; cell polarity; endocytosis; ENT1 gene; ENT2 gene; fungal gene; nonhuman; priority journal; protein domain; protein protein interaction; sequence homology; yeast; Adaptor Proteins, Signal Transducing; Carrier Proteins; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; Cell Polarity; Endocytosis; Genes, Fungal; Models, Molecular; Mutation; Phenotype; Protein Structure, Tertiary; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Eukaryota
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Epsins are endocytic proteins with a structured epsin N-terminal homology (ENTH) domain that binds phosphoinositides and a poorly structured C-terminal region that interacts with ubiquitin and endocytic machinery, including clathrin and endocytic scaffolding proteins. Yeast has two redundant genes encoding epsins, ENT1 and ENT2; deleting both genes is lethal. We demonstrate that the ENTH domain is both necessary and sufficient for viability of ent1Δent2Δ cells. Mutational analysis of the ENTH domain revealed a surface patch that is essential for viability and that binds guanine nucleotide triphosphatase-activating proteins for Cdc42, a critical regulator of cell polarity in all eukaryotes. Furthermore, the epsins contribute to regulation of specific Cdc42 signaling pathways in yeast cells. These data support a model in which the epsins function as spatial and temporal coordinators of endocytosis and cell polarity. © 2006 by The National Academy of Sciences of the USA.