Epsin ENTH domains perform an essential function regulating Cdc42 through binding Cdc42 GTPase Activating Proteins

R. C. AGUILAR, S.A. LONGHI, J.D. SHAW, L.-Y. YEH, S. KIN, A. SCHÖN, E. FREIRE, A. HSU, W.K. MCCORMICK, H.A. WATSON, B. WENDLAND

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

National Academy of Sciences

Lugar: Estados Unidos; Año: 2006 vol. 103 p. 4116 - 4121

0027-8424

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 ent1Deltaent2Delta 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.