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Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c


Insulin stimulates glucose uptake in muscle and adipocytes by signalling the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface1,2. The translocation of GLUT4 may involve signalling pathways that are both independent of and dependent on phosphatidylinositol-3-OH kinase (PI(3)K)3,4,5. This translocation also requires the actin cytoskeleton6,7,8, and the rapid movement of GLUT4 along linear tracks may be mediated by molecular motors9. Here we report that the unconventional myosin Myo1c is present in GLUT4-containing vesicles purified from 3T3-L1 adipocytes. Myo1c, which contains a motor domain, three IQ motifs and a carboxy-terminal cargo domain, is highly expressed in primary and cultured adipocytes. Insulin enhances the localization of Myo1c with GLUT4 in cortical tubulovesicular structures associated with actin filaments, and this colocalization is insensitive to wortmannin. Insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane is augmented by the expression of wild-type Myo1c and inhibited by a dominant-negative cargo domain of Myo1c. A decrease in the expression of endogenous Myo1c mediated by small interfering RNAs inhibits insulin-stimulated uptake of 2-deoxyglucose. Thus, myosin Myo1c functions in a PI(3)K-independent insulin signalling pathway that controls the movement of intracellular GLUT4-containing vesicles to the plasma membrane.

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Figure 1: Insulin augments cortical Myoic localization in 3T3-L1 adipocytes.
Figure 2: Whole-mount electron microscopy of the peripheral region of an insulin-stimulated 3T3-L1 adipocyte.
Figure 3: Dominant-negative cargo domain of Myo1c but not Myo1b inhibits insulin-stimulated Myc–GLUT4–GFP translocation to the plasma membrane.
Figure 4: Inhibition of insulin-stimulated 2-deoxyglucose uptake in differentiated 3T3-L1 adipocytes by siRNA-mediated degradation of Myo1c mRNA.
Figure 5: Expression of Myo1c–YFP in differentiated 3T3-L1 adipocytes potentiates insulin-stimulated Myc–GLUT4–CFP translocation.


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We thank M. Bahler for the Tu49 antiserum; E. Coudrier for the Myo1b construct; P. Furcinitti for help with digital microscopy; J. Lescyk and G. Witman, G. Hendricks and the Core Proteomics Facility and the Core Electron Microscopy Facility of the NIH Diabetes and Endocrinology Research Center at the University of Massachusetts Medical School.

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Correspondence to Michael P. Czech.

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Bose, A., Guilherme, A., Robida, S. et al. Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c. Nature 420, 821–824 (2002).

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