Michael Mueckler, Ph.D.

Cell Biology and Physiology
Internal Medicine

Molecular Cell Biology Program

  • 314-362-4160

  • 314-362-4161

  • 314-362-7463

  • 8228

  • 416 McDonnell Sciences Building

  • mmueckler@wustl.edu

  • signal transduction, metabolism, diabetes, intracellular trafficking, glucose transport

  • Molecular biology of glucose transporters

Research Abstract:

We are using the methods of molecular biology to study the structure, biosynthesis, and regulation of the mammalian facilitated-diffusion glucose transporters (GT). Glucose transport across the plasma membrane is carried out by a family of glycoproteins that is expressed in a tissue-specific manner in mammals. One such GT is expressed specifically in muscle and fat, where its activity is increased in response to insulin. A disruption in the normal sensitivity of this transporter to insulin is a principal feature of type II diabetes, and one of our goals is to define this defect at the molecular level and to understand the mechanism of insulin action on glucose transport.

Current specific areas of investigation include: isolation and characterization of novel GT genes; construction of transgenic mouse models and gene disruption by homologous recombination to study the physiologic role of the different transporters; regulation of the GT by hormones, growth factors, and oncogenes; transfection and expression of human GT cDNAs in cultured cell lines in conjunction with in vitro mutagenesis of the cDNA in order to define informational sequences within the GT molecule necessary for its proper intracellular targeting and response to insulin; structure-function studies involving expression of GT mRNAs in Xenopus oocytes; development of cell-free assays to study insulin signal transduction; and, analysis of the effect of HIV protease inhibitors on glucose transport.

Selected Publications:

Alisio A, Mueckler M. Relative proximity and orientation of helices 4 and 8 of the Glut1 glucose transporter. J Biol Chem. 2004 Jun 18;279(25):26540-5. Epub 2004 Apr 7.

Mueckler M, Makepeace C. Analysis of transmembrane Segment 8 of the Glut1 glucose gransporter by cysteine scanning mutagenesis and substituted cysteine accessibility. J Biol Chem 2004 279:10494-10499.

Hresko R, Murata H, Mueckler M. Phosphoinositide-dependent kinase-2 is a distinct protein kinase enriched in a novel cytoskeletal subcellular fraction associated with adipocyte plasma membranes. J Biol Chem 2003 278:21615-21622.

Murata H, Hresko R, Mueckler M. Reconstitution of PI 3-kinase-dependent insulin signaling in a cell-free system. J Biol Chem 2003 278:21607-21614.

Osman AA, Saito M, Makepeace C, et al. Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium. J Biol Chem 2003 278:52755–52762.

Last Updated: 8/4/2011 11:12:00 AM

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