The cytosolic C-terminus of the glucose transporter GLUT4 contains an acidic cluster endosomal targeting motif distal to the dileucine signal

Shewan, AM, Marsh, BJ, Melvin, DR, Martin, S, Gould, GW and James, DE (2000) The cytosolic C-terminus of the glucose transporter GLUT4 contains an acidic cluster endosomal targeting motif distal to the dileucine signal. Biochemical Journal, 350 1: 99-107. doi:10.1042/0264-6021:3500099


Author Shewan, AM
Marsh, BJ
Melvin, DR
Martin, S
Gould, GW
James, DE
Title The cytosolic C-terminus of the glucose transporter GLUT4 contains an acidic cluster endosomal targeting motif distal to the dileucine signal
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 2000
Sub-type Article (original research)
DOI 10.1042/0264-6021:3500099
Volume 350
Issue 1
Start page 99
End page 107
Total pages 9
Place of publication London
Publisher Portland Press
Collection year 2000
Language eng
Subject C1
780105 Biological sciences
270103 Protein Targeting and Signal Transduction
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Abstract The insulin-responsive glucose transporter GLUT4 is targeted to a post-endocytic compartment in adipocytes, from where it moves to the cell surface in response to insulin. Previous Studies have identified two cytosolic targeting motifs that regulate the intracellular sequestration of this protein: FQQI(5-8) in the N-terminus and LL489.490 (one-letter amino acid notation) in the C-terminus, In the present study we show that a GLUT4 chimaera in which the C-terminal 12 amino acids in GLUT4 have been replaced with the same region from human GLUT3 is constitutively targeted to the plasma membrane when expressed in 3T3-L1 adipocytes. To further dissect this domain it was divided into three regions, each of which was mutated en bloc to alanine residues. Analysis of these constructs revealed that the targeting information is contained within the residues TELEYLGP(498-505). Using the transferrin-horseradish peroxidase endosomal ablation technique in 3T3-L1 adipocytes, we show that mutants in which this C-terminal domain has been disrupted are more sensitive to chemical ablation than wild-type GLUT4. These data indicate that GLUT4 contains a targeting signal in its C-terminus, distal to the dileucine motif, that regulates its sorting into a post-endosomal compartment. Similar membrane-distal, acidic-cluster-based motifs are found in the cytosolic tails of the insulin-responsive aminopeptidase IRAP (insulin-regulated aminopeptidase) and the proprotein convertase PC6B, indicating that this type of motif may play an important role in the endosomal sequestration of a number of different proteins.
Keyword Biochemistry & Molecular Biology
Adipocyte
Endosome
Insulin
Trafficking
Translocation
Factor-ii Receptor
Golgi Network Localization
3t3-l1 Adipocytes
Intracellular Sequestration
Cytoplasmic Domain
Sorting Signals
Internalization Motif
Nh2 Terminus
Mdck Cells
Leucine
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 71 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 75 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 10 Jun 2008, 12:35:56 EST