| Title: | VPS21 encodes a rab5-like GTP binding protein that is required for the sorting of yeast vacuolar proteins |
| Author(s): | Horazdovsky BF; Busch GR; Emr SD; |
| Address: | "Division of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla 92093-0668" |
| DOI: | 10.1002/j.1460-2075.1994.tb06382.x |
| ISSN/ISBN: | 0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking) |
| Abstract: | "Many of the vacuolar protein sorting (vps) mutants of Saccharomyces cerevisiae exhibit severe defects in the sorting of vacuolar proteins but still retain near-normal vacuole morphology. The gene affected in one such mutant, vps21, has been cloned and found to encode a member of the ras-like GTP binding protein family. Sequence comparisons with other known GTP binding proteins indicate that Vps21p is unique but shares striking similarity with mammalian rab5 proteins (> 50% identity and > 70% similarity). Regions with highest similarity are clustered within the putative GTP binding motifs and the proposed effector domains of the Vps21/rab5 proteins. Point mutations constructed within these conserved regions inactivate Vps21p function; the mutant cells missort and secrete the soluble vacuolar hydrolase carboxypeptidase Y (CPY). Cells carrying a complete deletion of the VPS21 coding sequence (i) are viable but exhibit a growth defect at 38 degrees C, (ii) missort multiple vacuolar proteins, (iii) accumulate 40-50 nm vesicles and (iv) contain a large vacuole. VPS21 encodes a 22 kDa protein that binds GTP and fractionates with subcellular membranes. Mutant analysis indicates that the association with a membrane(s) is dependent on geranylgeranylation of the C-terminal cysteine residue(s) of Vps21p. We propose that Vps21p functions in the targeting and/or fusion of transport vesicles that mediate the delivery of proteins to the vacuole" |
| Keywords: | Amino Acid Sequence Animals Base Sequence Biological Transport Fungal Proteins/*metabolism GTP-Binding Proteins/*genetics/metabolism Mating Factor Membrane Proteins/genetics/metabolism Molecular Sequence Data Peptides/metabolism Point Mutation Restriction; |
| Notes: | "MedlineHorazdovsky, B F Busch, G R Emr, S D eng CA58689/CA/NCI NIH HHS/ GM-32703/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 1994/03/15 EMBO J. 1994 Mar 15; 13(6):1297-309. doi: 10.1002/j.1460-2075.1994.tb06382.x" |
