The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 25 Apr 2006
doi: 10.1242/jcs.02915
Research Article
Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure
Le Shen,
Eric D. Black,
Edwina D. Witkowski,
Wayne I. Lencer,
Vince Guerriero,
Eveline E. Schneeberger,
and
Jerrold R. Turner*
* Author for correspondence (e-mail: jturner{at}bsd.uchicago.edu)
Epithelial tight junctions form a barrier against passive paracellular flux. This barrier is regulated by complex physiologic and pathophysiologic signals that acutely fine-tune tight junction permeability. Although actomyosin contraction and myosin light chain phosphorylation are clearly involved in some forms of tight junction regulation, the contributions of other signaling events and the role of myosin light chain phosphorylation in this response are poorly understood. Here we ask if activation of myosin light chain kinase alone is sufficient to induce downstream tight junction regulation. We use a confluent polarized intestinal epithelial cell model system in which constitutively active myosin light chain kinase, tMLCK, is expressed using an inducible promoter. tMLCK expression increases myosin light chain phosphorylation, reorganizes perijunctional F-actin, and increases tight junction permeability. TJ proteins ZO-1 and occludin are markedly redistributed, morphologically and biochemically, but effects on claudin-1 and claudin-2 are limited. tMLCK inhibition prevents changes in barrier function and tight junction organization induced by tMLCK expression, suggesting that these events both require myosin light chain phosphorylation. We conclude that myosin light chain phosphorylation alone is sufficient to induce tight junction regulation and provide new insights into the molecular mechanisms that mediate this regulation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Terry, M. Nie, K. Matter, and M. S. Balda
Rho Signaling and Tight Junction Functions
Physiology,
February 1, 2010;
25(1):
16 - 26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Abouhamed, K. Grobe, I. V. Leefa Chong San, S. Thelen, U. Honnert, M. S. Balda, K. Matter, and M. Bahler
Myosin IXa Regulates Epithelial Differentiation and Its Deficiency Results in Hydrocephalus
Mol. Biol. Cell,
December 15, 2009;
20(24):
5074 - 5085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. S. Conlin, X. Wu, C. Nguyen, C. Dai, B. A. Vallance, A. M. J. Buchan, L. Boyer, and K. Jacobson
Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis
Am J Physiol Gastrointest Liver Physiol,
October 1, 2009;
297(4):
G735 - G750.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Van Itallie, A. S. Fanning, A. Bridges, and J. M. Anderson
ZO-1 Stabilizes the Tight Junction Solute Barrier through Coupling to the Perijunctional Cytoskeleton
Mol. Biol. Cell,
September 1, 2009;
20(17):
3930 - 3940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vojdani and J. Lambert
The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II
Evid. Based Complement. Altern. Med.,
July 21, 2009;
(2009)
nep063v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Lamprecht, C.-J. Hsieh, S. Lissner, L. Nold, A. Heil, V. Gaco, J. Schafer, J. R. Turner, and M. Gregor
Intestinal Anion Exchanger Down-regulated in Adenoma (DRA) Is Inhibited by Intracellular Calcium
J. Biol. Chem.,
July 17, 2009;
284(29):
19744 - 19753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ponsaerts, C. D'hondt, G. Bultynck, S. P. Srinivas, J. Vereecke, and B. Himpens
The Myosin II ATPase Inhibitor Blebbistatin Prevents Thrombin-Induced Inhibition of Intercellular Calcium Wave Propagation in Corneal Endothelial Cells
Invest. Ophthalmol. Vis. Sci.,
November 1, 2008;
49(11):
4816 - 4827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Gill, L. Shen, J. R. Turner, S. Saksena, W. A. Alrefai, N. Pant, A. Esmaili, A. Dwivedi, K. Ramaswamy, and P. K. Dudeja
Serotonin modifies cytoskeleton and brush-border membrane architecture in human intestinal epithelial cells
Am J Physiol Gastrointest Liver Physiol,
October 1, 2008;
295(4):
G700 - G708.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Kawedia, M. Jiang, A. Kulkarni, H. E. Waechter, K. S. Matlin, G. M. Pauletti, and A. G. Menon
The Protein Kinase A Pathway Contributes to Hg2+-Induced Alterations in Phosphorylation and Subcellular Distribution of Occludin Associated with Increased Tight Junction Permeability of Salivary Epithelial Cell Monolayers
J. Pharmacol. Exp. Ther.,
September 1, 2008;
326(3):
829 - 837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Khan
Acanthamoeba and the blood-brain barrier: the breakthrough
J. Med. Microbiol.,
September 1, 2008;
57(9):
1051 - 1057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Al-Sadi, D. Ye, K. Dokladny, and T. Y. Ma
Mechanism of IL-1{beta}-Induced Increase in Intestinal Epithelial Tight Junction Permeability
J. Immunol.,
April 15, 2008;
180(8):
5653 - 5661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Fries, C. Muja, C. Crisafulli, S. Cuzzocrea, and E. Mazzon
Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies
Am J Physiol Gastrointest Liver Physiol,
April 1, 2008;
294(4):
G938 - G947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Behling-Kelly, D. McClenahan, K. S. Kim, and C. J. Czuprynski
Viable "Haemophilus somnus" Induces Myosin Light-Chain Kinase-Dependent Decrease in Brain Endothelial Cell Monolayer Resistance
Infect. Immun.,
September 1, 2007;
75(9):
4572 - 4581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. N. Samarin, A. I. Ivanov, G. Flatau, C. A. Parkos, and A. Nusrat
Rho/Rho-associated Kinase-II Signaling Mediates Disassembly of Epithelial Apical Junctions
Mol. Biol. Cell,
September 1, 2007;
18(9):
3429 - 3439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D'hondt, S. P. Srinivas, J. Vereecke, and B. Himpens
Adenosine Opposes Thrombin-Induced Inhibition of Intercellular Calcium Wave in Corneal Endothelial Cells
Invest. Ophthalmol. Vis. Sci.,
April 1, 2007;
48(4):
1518 - 1527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G Buret
Mechanisms of epithelial dysfunction in giardiasis
Gut,
March 1, 2007;
56(3):
316 - 317.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D'hondt, R. Ponsaerts, S. P. Srinivas, J. Vereecke, and B. Himpens
Thrombin Inhibits Intercellular Calcium Wave Propagation in Corneal Endothelial Cells by Modulation of Hemichannels and Gap Junctions
Invest. Ophthalmol. Vis. Sci.,
January 1, 2007;
48(1):
120 - 133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Turner
Molecular Basis of Epithelial Barrier Regulation: From Basic Mechanisms to Clinical Application
Am. J. Pathol.,
December 1, 2006;
169(6):
1901 - 1909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. V. Graham, F. Wang, D. R. Clayburgh, J. X. Cheng, B. Yoon, Y. Wang, A. Lin, and J. R. Turner
Tumor Necrosis Factor-induced Long Myosin Light Chain Kinase Transcription Is Regulated by Differentiation-dependent Signaling Events: CHARACTERIZATION OF THE HUMAN LONG MYOSIN LIGHT CHAIN KINASE PROMOTER
J. Biol. Chem.,
September 8, 2006;
281(36):
26205 - 26215.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
