The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity

Thomas, Elaine C., Zhe, Yang, Molero, Juan Carlos, Schmitz-Peiffer, Carsten, Ramm, Georg, James, David E. and Whitehead, Jonathan P. (2006) The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity. International Journal of Biochemistry & Cell Biology, 38 10: 1686-1699. doi:10.1016/j.biocel.2006.03.009


Author Thomas, Elaine C.
Zhe, Yang
Molero, Juan Carlos
Schmitz-Peiffer, Carsten
Ramm, Georg
James, David E.
Whitehead, Jonathan P.
Title The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity
Journal name International Journal of Biochemistry & Cell Biology   Check publisher's open access policy
ISSN 1357-2725
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1016/j.biocel.2006.03.009
Volume 38
Issue 10
Start page 1686
End page 1699
Total pages 14
Editor G. J. Laurent
Place of publication UK
Publisher Pergamon
Language eng
Subject C1
320303 Medical Biochemistry - Lipids
730105 Endocrine organs and diseases (incl. diabetes)
Abstract Efficient insulin action requires spatial and temporal coordination of signaling cascades. The prototypical insulin receptor substrate, IRS-1 plays a central role in insulin signaling. By subcellular fractionation IRS-1 is enriched in a particulate fraction, termed the high speed pellet (HSP), and its redistribution from this fraction is associated with signal attenuation and insulin resistance. Anecdotal evidence suggests the cytoskeleton may underpin the localization of IRS-1 to the HSP. In the present study we have taken a systematic approach to examine whether the cytoskeleton contributes to the subcellular fractionation properties and function of IRS-1. By standard microscopy or immunoprecipitation we were unable to detect evidence to support a specific interaction between IRS-1 and the major cytoskeletal components actin (microfilaments), vimentin (intermediate filaments), and tubulin (microtubules) in 3T3-L1 adipocytes or in CHO.IR.IRS-1 cells. Pharmacological disruption of microfilaments and microtubules, individually or in combination, was without effect on the subcellular distribution of IRS-1 or insulin-stimulated tyrosine phosphorylation in either cell type. Phosphorylation of Akt was modestly reduced (20-35%) in 3T3-L1 adipocytes but not in CHO.IR.IRS-1 cells. In cells lacking intermediate filaments (Vim(-/-)) IRS-1 expression, distribution and insulin-stimulated phosphorylation appeared normal. Even after depolymerisation of microfilaments and microtubules, insulin-stimulated phosphorylation of IRS-1 and Akt were maintained in Vim-/- cells. Taken together these data indicate that the characteristic subcellular fractionation properties and function of IRS-1 are unlikely to be mediated by cytoskeletal networks and that proximal insulin signaling does not require an intact cytoskeleton. (c) 2006 Elsevier Ltd. All rights reserved.
Keyword Biochemistry & Molecular Biology
Cell Biology
Insulin
Signaling
Cytoskeleton
Glucose
Diabetes
Stimulated Glucose-transport
Protein-kinase-b
3t3-l1 Adipocytes
Glut4 Translocation
Phosphatidylinositol 3-kinase
Skeletal-muscle
Growth-factor
Phosphoinositide 3-kinase
Signal-transduction
Actin Cytoskeleton
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 20:00:38 EST