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First published online 6 May 2008
doi: 10.1242/jcs.015842

Journal of Cell Science 121, 1803-1814 (2008)
Published by The Company of Biologists 2008
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Research Article

Myosin II regulates the shape of three-dimensional intestinal epithelial cysts

Andrei I. Ivanov1,*,{ddagger}, Ann M. Hopkins2, G. Thomas Brown1, Kirsten Gerner-Smidt1, Brian A. Babbin1, Charles A. Parkos1 and Asma Nusrat1

1 Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
2 Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland

{ddagger} Author for correspondence (e-mail: Andrei_Ivanov{at}urmc.rochester.edu)

Accepted 3 March 2008

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.

Key words: Actin polymerization, phospholipase C, ADF/cofilin, Microtubules, Protrusions, Morphogenesis, Tubulogenesis, Matrigel






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