HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/G983    most recent 00356.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Ray, R. M. Articles by Johnson, L. R. Search for Related Content PubMed PubMed Citation Articles by Ray, R. M. Articles by Johnson, L. R.

MUCOSAL BIOLOGY

Role of myosin regulatory light chain and Rac1 in the migration of polyamine-depleted intestinal epithelial cells

Department of Physiology, The University of Tennessee Health Science Center, Memphis, Tennessee

Submitted 2 August 2006 ; accepted in final form 9 December 2006

We have previously shown that polyamine depletion decreased migration, Rac activation, and protein serine threonine phosphatase 2A activity. We have also shown that polyamine depletion increased cortical F-actin and decreased lamellipodia and stress fibers. In this study, we used staurosporine (STS), a potent, cell-permeable, and broad-spectrum serine/threonine kinase inhibitor, and studied migration. STS concentrations above 100 nM induced apoptosis. However, in polyamine-depleted cells, a lower concentration of STS (5 nM) increased attachment, spreading, Rac1 activation, and, subsequently, migration without causing apoptosis. STS-induced migration was completely prevented by a Rac1 inhibitor (NSC-23766) and dominant negative Rac1. These results imply that STS restores migration in polyamine-depleted cells through Rac1. The most important finding in this study was that polyamine depletion increased the association of phosphorylated myosin regulatory light chain (pThr¹⁸/Ser¹⁹-MRLC) at the cell periphery, which colocalized with thick cortical F-actin. Localization of pThr¹⁸- and pSer¹⁹-MRLC was found with stress fibers and nuclei, respectively. STS decreased the phosphorylation of cellular and peripheral pThr¹⁸-MRLC without any effect on nuclear pSer¹⁹-MRLC, dissolved thick cortical F-actin, and increased lamellipodia and stress fiber formation in polyamine-depleted cells. In control and polyamine-depleted cells, focal adhesion kinase (FAK) colocalized with stress fibers and the actin cortex, respectively. STS reorganized FAK, paxillin, and the cytoskeleton. These results suggest that polyamine depletion prevents the dephosphorylation of MRLC and thereby prevents the dynamic reorganization of the actin cytoskeleton and decreases lamellipodia formation resulting in the inhibition of migration.

putrescine; -difluoromethylornithine; F-actin; focal adhesion kinase; paxillin

This article has been cited by other articles:

				J. N. Rao, S. V. Liu, T. Zou, L. Liu, L. Xiao, X. Zhang, E. Bellavance, J. X.-J. Yuan, and J.-Y. Wang Rac1 promotes intestinal epithelial restitution by increasing Ca2+ influx through interaction with phospholipase C-{gamma}1 after wounding Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1499 - C1509. [Abstract] [Full Text] [PDF]