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Molecular and Cellular Biology, November 2009, p. 6128-6139, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.00815-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Role for Dynein in the Inhibition of Germ Cell Proliferative Fate{triangledown}

Maia Dorsett and Tim Schedl*

Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, 63110

Received 23 June 2009/ Returned for modification 24 July 2009/ Accepted 8 September 2009

During normal development as well as in diseased states such as cancer, extracellular "niches" often provide cues to proximal cells and activate intracellular pathways. Activation of such signaling pathways in turn instructs cellular proliferation and differentiation. In the Caenorhabditis elegans gonad, GLP-1/Notch signaling instructs germ line stem cells to self-renew through mitotic cell division. As germ cells progressively move out of the niche, they differentiate by entering meiosis and eventually form gametes. In this model system, we uncovered an unexpected role for the dynein motor complex in promoting normal differentiation of proliferating germ cells. We demonstrate that dynein light chain 1 (DLC-1) and its partner, dynein heavy chain 1, inhibit the proliferative cell fate, in part through regulation of METT-10, a conserved putative methyltransferase. We show that DLC-1 physically interacts with METT-10 and promotes both its overall levels and nuclear accumulation. Our results add a new dimension to the processes controlled by the dynein motor complex, demonstrating that dynein can act as an antiproliferative factor.


* Corresponding author. Mailing address: 4566 Scott Avenue, Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110. Phone: (314) 362-6162. Fax: (314) 362-7855. E-mail: ts{at}genetics.wustl.edu

{triangledown} Published ahead of print on 14 September 2009.


Molecular and Cellular Biology, November 2009, p. 6128-6139, Vol. 29, No. 22
0270-7306/09/$08.00+0     doi:10.1128/MCB.00815-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.