Peer Reviewed

1

Document Type

Article

Publication Date

1-6-2008

Keywords

Actins, Caco-2 Cells, Cell Polarity, Cell Shape, Cofilin 1, Down-Regulation, Epithelial Cells, Heterocyclic Compounds with 4 or More Rings, Humans, Intestinal Mucosa, Microfilaments, Myosin Type II, Nocodazole, Organ Culture Techniques, Polymers, RNA Stability, Type C Phospholipases

Comments

This article is available from http://jcs.biologists.org

Abstract

The development of luminal organs begins with the formation of spherical cysts composed of a single layer of epithelial cells. Using a model three-dimensional cell culture, this study examines the role of a cytoskeletal motor, myosin II, in cyst formation. Caco-2 and SK-CO15 intestinal epithelial cells were embedded into Matrigel, and myosin II was inhibited by blebbistatin or siRNA-mediated knockdown. Whereas control cells formed spherical cysts with a smooth surface, inhibition of myosin II induced the outgrowth of F-actin-rich surface protrusions. The development of these protrusions was abrogated after inhibition of F-actin polymerization or of phospholipase C (PLC) activity, as well as after overexpression of a dominant-negative ADF/cofilin. Surface protrusions were enriched in microtubules and their formation was prevented by microtubule depolymerization. Myosin II inhibition caused a loss of peripheral F-actin bundles and a submembranous extension of cortical microtubules. Our findings suggest that inhibition of myosin II eliminates the cortical F-actin barrier, allowing microtubules to reach and activate PLC at the plasma membrane. PLC-dependent stimulation of ADF/cofilin creates actin-filament barbed ends and promotes the outgrowth of F-actin-rich protrusions. We conclude that myosin II regulates the spherical shape of epithelial cysts by controlling actin polymerization at the cyst surface.

Disciplines

Surgery

Citation

Ivanov AI, Hopkins AM, Brown GT, Gerner-Smidt K, Babbin BA, Parkos CA, Nusrat A. Myosin II regulates the shape of three-dimensional intestinal epithelial cysts. Journal of Cell Science. 2008;121(Pt 11):1803-14.

PubMed ID

18460584

DOI Link

10.1242/jcs.015842

Included in

Surgery Commons

Share

COinS