Primary Cilia Regulates the Directional Migration and Barrier Integrity of Endothelial Cells Through the Modulation of hsp27 Dependent Actin Cytoskeletal Organization

Authors

Thomas J. Jones, Northeastern UniversityFollow
Ravi K. Adapala, Northeastern University
Werner J. Geldenhuys, Northeastern University
Chris Bursley, Northeastern University
Wissam A. AbouAlaiwi, University of ToledoFollow
Surya M. Nauli, Chapman UniversityFollow
Charles K. Thodeti, Northeastern University

Document Type

Article

Publication Date

1-2012

Abstract

Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737orpk/orpk) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild type. In contrast, endothelial cells from polycystin-1 deficient mice (pkd1null/null), with impaired cilia function, display robust stress fibers and focal adhesion assembly. We found that the Tg737orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared to the wild type and pkd1null/null cells. Finally, we found that the expression of heat shock protein 27 (hsp27) and the phosphorylation of FAK are down regulated in the Tg737orpk/orpk cells and overexpression of hsp27 restored both FAK phosphorylation and cell migration. Taken together, these results demonstrate that disruption of the primary cilia structure or function compromises the endothelium through the suppression of hsp27 dependent actin organization and focal adhesion formation, which may contribute to the vascular dysfunction in ciliopathies.

Comments

This is the accepted version of the following article:

Jones TJ, Adapala RK, Geldenhuys WJ, Bursley C, AbouAlaiwi WA, Nauli SM, Thodeti CK. Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization. J Cell Physiol. 2012 Jan;227(1):70-6.

which has been published in final form at DOI: 10.1002/jcp.22704.

Recommended Citation

Jones TJ, Adapala RK, Geldenhuys WJ, Bursley C, AbouAlaiwi WA, Nauli SM, Thodeti CK. Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization. J Cell Physiol. 2012 Jan;227(1):70-6. doi: 10.1002/jcp.22704

Copyright

Wiley