You are not logged in.

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 and cell biology, vol. 38, no. 10, pp. 1686-1699, doi: 10.1016/j.biocel.2006.03.009.

Attached Files
Name Description MIMEType Size Downloads

Title The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity
Author(s) Thomas, Elaine. C.
Zhe, Yang
Molero, Juan Carlos
Schmitz-Peiffer, Carsten
Ramm, Georg
James, David E.
Whitehead, Jonathan P.
Journal name International journal of biochemistry and cell biology
Volume number 38
Issue number 10
Start page 1686
End page 1699
Publisher Pergamon
Place of publication Exeter, England
Publication date 2006
ISSN 1357-2725
1878-5875
Keyword(s) insulin
signaling
cytoskeleton
glucose
diabetes
Summary 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.
Language eng
DOI 10.1016/j.biocel.2006.03.009
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009186

Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in TR Web of Science
Scopus Citation Count Cited 8 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 510 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Mon, 13 Oct 2008, 15:53:42 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.