Ma. Lampson et al., Insulin-regulated release from the endosomal recycling compartment is regulated by budding of specialized vesicles, MOL BIOL CE, 12(11), 2001, pp. 3489-3501
In several cell types, specific membrane proteins are retained intracellula
rly and rapidly redistributed to the surface in response to stimulation. In
fat and muscle, the GLUT4 glucose transporter is dynamically retained beca
use it is rapidly internalized and slowly recycled to the plasma membrane.
Insulin increases the recycling of GLUT4, resulting in a net translocation
to the surface. We have shown that fibroblasts also have an insulin-regulat
ed recycling mechanism. Here we show that GLUT4 is retained within the tran
sferrin receptor-containing general endosomal recycling compartment in Chin
ese hamster ovary (CHO) cells rather than being segregated to a specialized
, GLUT4-recycling compartment. With the use of total internal reflection mi
croscopy, we demonstrate that the TR and GLUT4 are transported from the per
icentriolar recycling compartment in separate vesicles. These data provide
the first functional evidence for the formation of distinct classes of vesi
cles from the recycling compartment. We propose that GLUT4 is dynamically r
etained within the endosomal recycling compartment in CHO cells because it
is concentrated in vesicles that form more slowly than those that transport
TR. In 3T3-L1 adipocytes, cells that naturally express GLUT4, we find that
GLUT4 is partially segregated to a separate compartment that is inaccessib
le to the TR. We present a model for the formation of this specialized comp
artment in fat cells, based on the general mechanism described in CHO cells
, which may explain the increased retention of GLUT4 and its insulin-induce
d translocation in fat cells.