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Vol. 13, Issue 7, 2421-2435, July 2002
and
*Department of Biochemistry and Insulin regulates glucose uptake into fat and muscle by modulating
the distribution of the GLUT4 glucose transporter between the surface
and interior of cells. The GLUT4 trafficking pathway overlaps with the
general endocytic recycling pathway, but the degree and functional
significance of the overlap are not known. In this study of intact
adipocytes, we demonstrate, by using a compartment-specific
fluorescence-quenching assay, that GLUT4 is equally distributed between
two intracellular pools: the transferrin receptor-containing
endosomes and a specialized compartment that excludes the transferrin
receptor. These pools of GLUT4 are in dynamic communication with one
another and with the cell surface. Insulin-induced redistribution of
GLUT4 to the surface requires mobilization of both pools. These data
establish a role for the general endosomal system in the specialized,
insulin-regulated trafficking of GLUT4. Trafficking through the general
endosomal system is regulated by rab11. Herein, we show that rab11 is
required for the transport of GLUT4 from endosomes to the specialized
compartment and for the insulin-induced translocation to the cell
surface, emphasizing the importance of the general endosomal pathway in the specialized trafficking of GLUT4. Based on these findings we
propose a two-step model for GLUT4 trafficking in which the general
endosomal recycling compartment plays a specialized role in the
insulin-regulated traffic of GLUT4. This compartment-based model
provides the framework for understanding insulin-regulated trafficking
at a molecular level.
Program in
Physiology, Biophysics and Molecular Medicine, Weill Medical College of
Cornell University, New York, New York 10021; and
Department of Cell Biology, New York University School
of Medicine, New York, New York 10016-6437
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