A dual role of the N-terminal FQQI motif in GLUT4 trafficking.

In adipocytes, the glucose transporter GLUT4 recycles between intracellular storage vesicles and the plasma membrane. GLUT4 is internalized by a clathrin- and dynamin-dependent mechanism, and sorted into an insulin-sensitive storage compartment. Insulin stimulation leads to GLUT4 accumulation on the cell surface. The N-terminal F5QQI motif in GLUT4 has been shown ...
previously to be required for sorting of the protein in the basal state. Here, we show that the FQQI motif is a binding site for the medium chain adaptin micro1, a subunit of the AP-1 adaptor complex that plays a role in post-Golgi/endosomal trafficking events. In order to investigate the role of AP-1 and AP-2 in GLUT4 trafficking, we generated 3T3-L1 adipocytes expressing HA-GLUT4-GFP and knocked down the AP-1 and AP-2 complex by RNAi, respectively. In AP-1 and AP-2 knockdown adipocytes, GLUT4 accumulates at the cell surface in the basal state, consistent with a role of AP-1 in post-endosomal sorting of GLUT4 to the insulin-sensitive storage compartment, and of AP-2 in clathrin-mediated endocytosis. Our data demonstrate a dual role of the F5QQI motif and support the conclusion that the AP complexes direct GLUT4 trafficking and endocytosis.
Mesh Terms:
3T3-L1 Cells, Amino Acid Motifs, Amino Acid Sequence, Animals, Base Sequence, Endosomes, Genetic Vectors, Glucose Transporter Type 4, Humans, Lentivirus, Mice, Protein Binding, Protein Transport, RNA, Small Interfering, Sequence Alignment, Transcription Factor AP-1, Transcription Factor AP-2
Biol. Chem.
Date: Sep. 01, 2009
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