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Mol Biol Cell

Title:		Domains of the Rsp5 ubiquitin-protein ligase required for receptor-mediated and fluid-phase endocytosis
Author(s):		Dunn R; Hicke L;
Address:		"Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA"
Journal Title:		Mol Biol Cell
Year:		2001
Volume:		12
Issue:		2
Page Number:		421 - 435
DOI:		10.1091/mbc.12.2.421
ISSN/ISBN:		1059-1524 (Print) 1059-1524 (Linking)
Abstract:		"Yeast Rsp5p and its mammalian homologue, Nedd4, are hect domain ubiquitin-protein ligases (E3s) required for the ubiquitin-dependent endocytosis of plasma membrane proteins. Because ubiquitination is sufficient to induce internalization, E3-mediated ubiquitination is a key regulatory event in plasma membrane protein endocytosis. Rsp5p is an essential, multidomain protein containing an amino-terminal C2 domain, three WW protein-protein interaction domains, and a carboxy-terminal hect domain that carries E3 activity. In this study, we demonstrate that Rsp5p is peripherally associated with membranes and provide evidence that Rsp5p functions as part of a multimeric protein complex. We define the function of Rsp5p and its domains in the ubiquitin-dependent internalization of the yeast alpha-factor receptor, Ste2p. Temperature-sensitive rsp5 mutants were unable to ubiquitinate or to internalize Ste2p at the nonpermissive temperature. Deletion of the entire C2 domain had no effect on alpha-factor internalization; however, point mutations in any of the three WW domains impaired both receptor ubiquitination and internalization. These observations indicate that the WW domains play a role in the important regulatory event of selecting phosphorylated proteins as endocytic cargo. In addition, mutations in the C2 and WW1 domains had more severe defects on transport of fluid-phase markers to the vacuole than on receptor internalization, suggesting that Rsp5p functions at multiple steps in the endocytic pathway"
Keywords:		Amino Acid Sequence Binding Sites Catalytic Domain Cell Membrane/metabolism Endocytosis/*physiology Endosomal Sorting Complexes Required for Transport Isoquinolines/metabolism Ligases/genetics/*metabolism Mating Factor Membrane Proteins/genetics/metabolis;
Notes:		"MedlineDunn, R Hicke, L eng R01 DK053257/DK/NIDDK NIH HHS/ T32 GM008061/GM/NIGMS NIH HHS/ DK 53257/DK/NIDDK NIH HHS/ T32GM08061/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2001/02/17 Mol Biol Cell. 2001 Feb; 12(2):421-35. doi: 10.1091/mbc.12.2.421"