Rab5 Activation by the Vps9 Domain

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Title: Rab5 Activation by the Vps9 Domain
Author: Carney, Darren Scott
Abstract: The movement of proteins through the endocytic pathway is a complex and highly regulated process . Not only is this pathway used to internalize cellular nutrients , but it is also used to modulate a cell's response to extracellular stimuli . Internalization and subsequent trafficking of transmembrane receptor proteins that receive these signals from the external milieu play an essential role in establishing and maintaining cellular homeostasis . As key regulators of the early stages the endocytic pathway , the small GTPases of the Rab5 family serve an essential function in integrating intracellular protein traffic and these cell signaling events . Rab5 proteins exert their influence on protein trafficking only when bound to GTP . A large family of proteins containing a conserved domain (Vps9 ) activate Rab5 by promoting the release of GDP and reloading of GTP . These nucleotide exchange factors contain additional domains which link them to specific cellular locations or signaling cascades . The multiplicity of these Rab5 proteins and exchange factors raises the question of how these proteins specifically interact to regulate individual trafficking events . To investigate this specificity , the three Rab5 proteins of Saccharomyces cerevisiae , Vps21 , Ypt52 and Ypt53 , and the two yeast Vps9 domain -containing proteins , Vps9 and Muk1 , were analyzed . This analysis identified previously unappreciated roles for Ypt53 and Muk1 in a relatively late stage of endocytosis . A mutational analysis of Vps9 identified several residues important for Vps9 domain function and shed light on a possible intramolecular regulation of this domain by the carboxy -terminal ubiquitin -binding CUE domain . Finally , structural studies of the Rab5 /Vps9 domain complex were initiated to gain a better understanding of the molecular mechanisms by which Rab5 proteins interact with and are activated by the Vps9 domain .
URI: http : / /hdl .handle .net /2152 .5 /252
Date: 2007-05-21


Rab5 Activation by the Vps9 Domain. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /252 .

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