Psidin, a conserved protein that regulates protrusion dynamics and cell migration
- Ji Hoon Kim1,
- Aeri Cho1,
- Hongyan Yin1,
- Dorothy A. Schafer2,3,
- Ghassan Mouneimne4,
- Kaylene J. Simpson4,
- Kim-Vy Nguyen4,
- Joan S. Brugge4 and
- Denise J. Montell1,5
- 1Department of Biological Chemistry, Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA;
- 2Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA;
- 3Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22904, USA;
- 4Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Abstract
Dynamic assembly and disassembly of actin filaments is a major driving force for cell movements. Border cells in the Drosophila ovary provide a simple and genetically tractable model to study the mechanisms regulating cell migration. To identify new genes that regulate cell movement in vivo, we screened lethal mutations on chromosome 3R for defects in border cell migration and identified two alleles of the gene psidin (psid). In vitro, purified Psid protein bound F-actin and inhibited the interaction of tropomyosin with F-actin. In vivo, psid mutations exhibited genetic interactions with the genes encoding tropomyosin and cofilin. Border cells overexpressing Psid together with GFP-actin exhibited altered protrusion/retraction dynamics. Psid knockdown in cultured S2 cells reduced, and Psid overexpression enhanced, lamellipodial dynamics. Knockdown of the human homolog of Psid reduced the speed and directionality of migration in wounded MCF10A breast epithelial monolayers, whereas overexpression of the protein increased migration speed and altered protrusion dynamics in EGF-stimulated cells. These results indicate that Psid is an actin regulatory protein that plays a conserved role in protrusion dynamics and cell migration.
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Footnotes
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↵5 Corresponding author.
E-MAIL dmontell{at}jhmi.edu; FAX (410) 955-5759.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.2028611.
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Supplemental material is available for this article.
- Received January 4, 2011.
- Accepted February 11, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press