![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on February 1, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 23, 2003
Revised on October 7, 2003
Accepted on October 7, 2003
1 Department of Biochemistry, and Program in Biochemistry and Structural Biology, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021
* Corresponding author. E-mail address: temcgraw{at}med.cornell.edu.
The intracellularly stored GLUT4 glucose transporter is rapidly translocated to the cell surface upon insulin stimulation. Regulation of GLUT4 distribution is key for the maintenance of whole body glucose homeostasis. We find that GLUT4 is excluded from the plasma membrane of adipocytes by a dynamic retention/retrieval mechanism. Our kinetic studies indicate that GLUT4-containing vesicles continually bud and fuse with endosomes in the absence of insulin, and that these GLUT4 vesicles are 5 times as likely to fuse with an endosome as with the plasma membrane. We hypothesize that this intracellular cycle of vesicle budding and fusion is an element of the active mechanism by which GLUT4 is retained. The GLUT4 trafficking pathway does not extensively overlap with that of furin, indicating that the trans Golgi network, a compartment in which furin accumulates, is not a significant storage reservoir of GLUT4. An intact microtubule cytoskeleton is required for insulin-stimulated recruitment to the cell surface, although it is not required for the basal budding/fusion cycle. Nocodazole disruption of the microtubule cytoskeleton reduces the insulin-stimulated exocytosis of GLUT4, accounting for the reduced insulin-stimulated translocation of GLUT4 to the cell surface.
This article has been cited by other articles:
|
|
 |
|
  E. Capilla, M. Diaz, J. C. Hou, J. V. Planas, and J. E. Pessin High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS160 inhibition in adipocytes Am J Physiol Endocrinol Metab, February 1, 2010; 298(2): E329 - E336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Fazakerley, G. D. Holman, A. Marley, D. E. James, J. Stockli, and A. C. F. Coster Kinetic Evidence for Unique Regulation of GLUT4 Trafficking by Insulin and AMP-activated Protein Kinase Activators in L6 Myotubes J. Biol. Chem., January 15, 2010; 285(3): 1653 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Esk, C.-Y. Chen, L. Johannes, and F. M. Brodsky The clathrin heavy chain isoform CHC22 functions in a novel endosomal sorting step J. Cell Biol., January 11, 2010; 188(1): 131 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E Leney and J. M Tavare The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets J. Endocrinol., October 1, 2009; 203(1): 1 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Fazakerley, S. P. Lawrence, V. A. Lizunov, S. W. Cushman, and G. D. Holman A common trafficking route for GLUT4 in cardiomyocytes in response to insulin, contraction and energy-status signalling J. Cell Sci., March 1, 2009; 122(5): 727 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shi, G. Huang, and K. V. Kandror Self-assembly of Glut4 Storage Vesicles during Differentiation of 3T3-L1 Adipocytes J. Biol. Chem., October 31, 2008; 283(44): 30311 - 30321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Blot and T. E. McGraw Molecular Mechanisms Controlling GLUT4 Intracellular Retention Mol. Biol. Cell, August 1, 2008; 19(8): 3477 - 3487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. M. Song, R. C. Hresko, and M. Mueckler Identification of Amino Acid Residues within the C Terminus of the Glut4 Glucose Transporter That Are Essential for Insulin-stimulated Redistribution to the Plasma Membrane J. Biol. Chem., May 2, 2008; 283(18): 12571 - 12585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Larance, G. Ramm, and D. E. James The GLUT4 Code Mol. Endocrinol., February 1, 2008; 22(2): 226 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Williams and J. E. Pessin Mapping of R-SNARE function at distinct intracellular GLUT4 trafficking steps in adipocytes J. Cell Biol., January 28, 2008; 180(2): 375 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Muretta, I. Romenskaia, and C. C. Mastick Insulin Releases Glut4 from Static Storage Compartments into Cycling Endosomes and Increases the Rate Constant for Glut4 Exocytosis J. Biol. Chem., January 4, 2008; 283(1): 311 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Diaz, C. N. Antonescu, E. Capilla, A. Klip, and J. V. Planas Fish Glucose Transporter (GLUT)-4 Differs from Rat GLUT4 in Its Traffic Characteristics but Can Translocate to the Cell Surface in Response to Insulin in Skeletal Muscle Cells Endocrinology, November 1, 2007; 148(11): 5248 - 5257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Huang, L. M. Lifshitz, C. Jones, K. D. Bellve, C. Standley, S. Fonseca, S. Corvera, K. E. Fogarty, and M. P. Czech Insulin Stimulates Membrane Fusion and GLUT4 Accumulation in Clathrin Coats on Adipocyte Plasma Membranes Mol. Cell. Biol., May 1, 2007; 27(9): 3456 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shi and K. V. Kandror The Luminal Vps10p Domain of Sortilin Plays the Predominant Role in Targeting to Insulin-responsive Glut4-containing Vesicles J. Biol. Chem., March 23, 2007; 282(12): 9008 - 9016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yu, J. Cresswell, M. G. Loffler, and J. S. Bogan The Glucose Transporter 4-regulating Protein TUG Is Essential for Highly Insulin-responsive Glucose Uptake in 3T3-L1 Adipocytes J. Biol. Chem., March 9, 2007; 282(10): 7710 - 7722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Campanoni and M. R. Blatt Membrane trafficking and polar growth in root hairs and pollen tubes J. Exp. Bot., January 1, 2007; 58(1): 65 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Eyster, Q. S. Duggins, G. J. Gorbsky, and A. L. Olson Microtubule Network Is Required for Insulin Signaling through Activation of Akt/Protein Kinase B: EVIDENCE THAT INSULIN STIMULATES VESICLE DOCKING/FUSION BUT NOT INTRACELLULAR MOBILITY J. Biol. Chem., December 22, 2006; 281(51): 39719 - 39727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Williams, S. W. Hicks, C. E. Machamer, and J. E. Pessin Golgin-160 Is Required for the Golgi Membrane Sorting of the Insulin-responsive Glucose Transporter GLUT4 in Adipocytes Mol. Biol. Cell, December 1, 2006; 17(12): 5346 - 5355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Hou, N. Suzuki, J. E. Pessin, and R. T. Watson A Specific Dileucine Motif Is Required for the GGA-dependent Entry of Newly Synthesized Insulin-responsive Aminopeptidase into the Insulin-responsive Compartment J. Biol. Chem., November 3, 2006; 281(44): 33457 - 33466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Peck, S. Ye, V. Pham, R. N. Fernando, S. L. Macaulay, S. Y. Chai, and A. L. Albiston Interaction of the Akt Substrate, AS160, with the Glucose Transporter 4 Vesicle Marker Protein, Insulin-Regulated Aminopeptidase Mol. Endocrinol., October 1, 2006; 20(10): 2576 - 2583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gonzalez and T. E. McGraw Insulin Signaling Diverges into Akt-dependent and -independent Signals to Regulate the Recruitment/Docking and the Fusion of GLUT4 Vesicles to the Plasma Membrane Mol. Biol. Cell, October 1, 2006; 17(10): 4484 - 4493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Hou, S. Shigematsu, H. C. Crawford, P. Z. Anastasiadis, and J. E. Pessin Dual Regulation of Rho and Rac by p120 Catenin Controls Adipocyte Plasma Membrane Trafficking J. Biol. Chem., August 18, 2006; 281(33): 23307 - 23312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Martin, A. Lee, and T. E. McGraw GLUT4 Distribution between the Plasma Membrane and the Intracellular Compartments Is Maintained by an Insulin-modulated Bipartite Dynamic Mechanism J. Biol. Chem., January 6, 2006; 281(1): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishiki and A. Klip Minireview: Recent Developments in the Regulation of Glucose Transporter-4 Traffic: New Signals, Locations, and Partners Endocrinology, December 1, 2005; 146(12): 5071 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Larance, G. Ramm, J. Stockli, E. M. van Dam, S. Winata, V. Wasinger, F. Simpson, M. Graham, J. R. Junutula, M. Guilhaus, et al. Characterization of the Role of the Rab GTPase-activating Protein AS160 in Insulin-regulated GLUT4 Trafficking J. Biol. Chem., November 11, 2005; 280(45): 37803 - 37813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bose, A. Guilherme, S. Huang, A. C. Hubbard, C. R. Lane, N. A. Soriano, and M. P. Czech The v-SNARE Vti1a Regulates Insulin-stimulated Glucose Transport and Acrp30 Secretion in 3T3-L1 Adipocytes J. Biol. Chem., November 4, 2005; 280(44): 36946 - 36951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Usui, T. Imamura, J. L. Babendure, H. Satoh, J.-C. Lu, C. J. Hupfeld, and J. M. Olefsky G Protein-Coupled Receptor Kinase 2 Mediates Endothelin-1-Induced Insulin Resistance via the Inhibition of Both G{alpha}q/11 and Insulin Receptor Substrate-1 Pathways in 3T3-L1 Adipocytes Mol. Endocrinol., November 1, 2005; 19(11): 2760 - 2768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Li and K. V. Kandror Golgi-Localized, {gamma}-Ear-Containing, Arf-Binding Protein Adaptors Mediate Insulin-Responsive Trafficking of Glucose Transporter 4 in 3T3-L1 Adipocytes Mol. Endocrinol., August 1, 2005; 19(8): 2145 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Lizunov, H. Matsumoto, J. Zimmerberg, S. W. Cushman, and V. A. Frolov Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in rat adipose cells J. Cell Biol., May 9, 2005; 169(3): 481 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Eyster, Q. S. Duggins, and A. L. Olson Expression of Constitutively Active Akt/Protein Kinase B Signals GLUT4 Translocation in the Absence of an Intact Actin Cytoskeleton J. Biol. Chem., May 6, 2005; 280(18): 17978 - 17985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang and G. D. Holman Insulin and Contraction Stimulate Exocytosis, but Increased AMP-activated Protein Kinase Activity Resulting from Oxidative Metabolism Stress Slows Endocytosis of GLUT4 in Cardiomyocytes J. Biol. Chem., February 11, 2005; 280(6): 4070 - 4078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Randhawa, F. S.L. Thong, D. Y. Lim, D. Li, R. R. Garg, R. Rudge, T. Galli, A. Rudich, and A. Klip Insulin and Hypertonicity Recruit GLUT4 to the Plasma Membrane of Muscle Cells by Using N-Ethylmaleimide-sensitive Factor-dependent SNARE Mechanisms but Different v-SNAREs: Role of TI-VAMP Mol. Biol. Cell, December 1, 2004; 15(12): 5565 - 5573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sbrissa, O. C. Ikonomov, J. Strakova, and A. Shisheva Role for a Novel Signaling Intermediate, Phosphatidylinositol 5-Phosphate, in Insulin-Regulated F-Actin Stress Fiber Breakdown and GLUT4 Translocation Endocrinology, November 1, 2004; 145(11): 4853 - 4865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wertheim, Z. Cai, and T. E. McGraw The Transcription Factor CCAAT/Enhancer-binding Protein {alpha} Is Required for the Intracellular Retention of GLUT4 J. Biol. Chem., October 1, 2004; 279(40): 41468 - 41476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zeigerer, M. K. McBrayer, and T. E. McGraw Insulin Stimulation of GLUT4 Exocytosis, but Not Its Inhibition of Endocytosis, Is Dependent on RabGAP AS160 Mol. Biol. Cell, October 1, 2004; 15(10): 4406 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Guilherme, N. A. Soriano, P. S. Furcinitti, and M. P. Czech Role of EHD1 and EHBP1 in Perinuclear Sorting and Insulin-regulated GLUT4 Recycling in 3T3-L1 Adipocytes J. Biol. Chem., September 17, 2004; 279(38): 40062 - 40075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Khan, E. Capilla, J. C. Hou, R. T. Watson, J. R. Smith, and J. E. Pessin Entry of Newly Synthesized GLUT4 into the Insulin-responsive Storage Compartment Is Dependent upon Both the Amino Terminus and the Large Cytoplasmic Loop J. Biol. Chem., September 3, 2004; 279(36): 37505 - 37511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Govers, A. C. F. Coster, and D. E. James Insulin Increases Cell Surface GLUT4 Levels by Dose Dependently Discharging GLUT4 into a Cell Surface Recycling Pathway Mol. Cell. Biol., July 15, 2004; 24(14): 6456 - 6466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bose, S. Robida, P. S. Furcinitti, A. Chawla, K. Fogarty, S. Corvera, and M. P. Czech Unconventional Myosin Myo1c Promotes Membrane Fusion in a Regulated Exocytic Pathway Mol. Cell. Biol., June 15, 2004; 24(12): 5447 - 5458. [Abstract] [Full Text] [PDF]
|
|
