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Science 11 April 2008:
Vol. 320. no. 5873, pp. 239 - 243
DOI: 10.1126/science.1155313
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Reports

Leiomodin Is an Actin Filament Nucleator in Muscle Cells

David Chereau,1*{dagger} Malgorzata Boczkowska,2{dagger} Aneta Skwarek-Maruszewska,3 Ikuko Fujiwara,4 David B. Hayes,1 Grzegorz Rebowski,2 Pekka Lappalainen,3 Thomas D. Pollard,4 Roberto Dominguez2{ddagger}

Initiation of actin polymerization in cells requires nucleation factors. Here we describe an actin-binding protein, leiomodin, that acted as a strong filament nucleator in muscle cells. Leiomodin shared two actin-binding sites with the filament pointed end–capping protein tropomodulin: a flexible N-terminal region and a leucine-rich repeat domain. Leiomodin also contained a C-terminal extension of 150 residues. The smallest fragment with strong nucleation activity included the leucine-rich repeat and C-terminal extension. The N-terminal region enhanced the nucleation activity threefold and recruited tropomyosin, which weakly stimulated nucleation and mediated localization of leiomodin to the middle of muscle sarcomeres. Knocking down leiomodin severely compromised sarcomere assembly in cultured muscle cells, which suggests a role for leiomodin in the nucleation of tropomyosin-decorated filaments in muscles.

1 Boston Biomedical Research Institute, Watertown, MA 02472, USA.
2 Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
4 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.

* Present address: Elan Pharmaceuticals, San Francisco, CA 94080, USA.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: droberto{at}mail.med.upenn.edu

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