| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Discovery Research Laboratories II (H.T., I.K., H.H., N.K., K.Y., S.K., Y.F.), Pharmaceutical Research Division, Takeda Chemical Industries Co., Ltd., Tsukuba, Ibaraki 300-4293, Japan; and Department of Biochemistry (H.T., P.F.P.), Boston University School of Medicine, and AdipoGenix, Inc. (E.P., C.C.B., P.F.P.), Boston, Massachusetts 02118
Address all correspondence and requests for reprints to: Hideaki Tojo, Ph.D., Discovery Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries Co., Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan. E-mail: Tojo_Hideaki{at}takeda.co.jp.
Insulin stimulates translocation of glucose transporter isoform type 4 (GLUT4) and the insulin-responsive aminopeptidase (IRAP) from an intracellular storage pool to the plasma membrane in muscle and fat cells. A role for the cytoskeleton in insulin action has been postulated, and the insulin signaling pathway has been well investigated; however, the molecular mechanism by which GLUT4/IRAP-containing vesicles move from an interior location to the cell surface in response to insulin is incompletely understood. Here, we have screened for IRAP-binding proteins using a yeast two-hybrid system and have found that the C-terminal domain of FHOS (formin homolog overexpressed in spleen) interacts with the N-terminal cytoplasmic domain of IRAP. FHOS is a member of the Formin/Diaphanous family of proteins that is expressed most abundantly in skeletal muscle. In addition, there are two novel types of FHOS transcripts generated by alternative mRNA splicing. FHOS78 has a 78-bp insertion and it is expressed mainly in skeletal muscle where it may be the most abundant isoform in humans. The ubiquitously expressed FHOS24 has a 24-bp insertion encoding an in-frame stop codon that results in a truncated polypeptide. It is known that some formin family proteins interact with the actin-binding profilin proteins. Both FHOS and FHOS78 bound to profilin IIa via their formin homology 1 domains, but neither bound profilin I or IIb. Overexpression of FHOS and FHOS78 resulted in enhanced insulin-stimulated glucose uptake in L6 cells to similar levels. However, overexpression of FHOS24, lacking the IRAP-binding domain, did not affect insulin-stimulated glucose uptake. These findings suggest that FHOS mediates an interaction between GLUT4/IRAP-containing vesicles and the cytoskeleton and may participate in exocytosis and/or retention of this membrane compartment.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 T. Hosaka, C. C. Brooks, E. Presman, S.-K. Kim, Z. Zhang, M. Breen, D. N. Gross, E. Sztul, and P. F. Pilch p115 Interacts with the GLUT4 Vesicle Protein, IRAP, and Plays a Critical Role in Insulin-stimulated GLUT4 Translocation Mol. Biol. Cell, June 1, 2005; 16(6): 2882 - 2890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Gill, J. Roecklein-Canfield, D. R. Sage, M. Zambela-Soediono, N. Longtine, M. Uknis, and J. D. Fingeroth EBV attachment stimulates FHOS/FHOD1 redistribution and co-aggregation with CD21: formin interactions with the cytoplasmic domain of human CD21 J. Cell Sci., June 1, 2004; 117(13): 2709 - 2720. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
