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Vol. 16, Issue 10, 4648-4659, October 2005

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Mammalian Septins Regulate Microtubule Stability through Interaction with the Microtubule-binding Protein MAP4

Brandon E. Kremer ^*, Timothy Haystead , and Ian G. Macara ^*

^* Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710

Submitted April 4, 2005; Revised June 23, 2005; Accepted August 1, 2005
Monitoring Editor: David Drubin

Mammalian septins constitute a family of at least 12 GTP-binding proteins that can form hetero-oligomers and that are sometimes found in association with actin or microtubule filaments. However, their functions are not understood. Using RNA interference, we found that suppression of septin expression in HeLa cells caused a pronounced increase in microtubule stability. Mass spectroscopic analysis of proteins coprecipitating with Sept6 identified the microtubule-associated protein MAP4 as a septin binding partner. A small, proline-rich region in the C-terminal half of MAP4 bound directly to a Sept 2:6:7 heterotrimer, and to the Sept2 monomer. The trimer blocked the ability of this MAP4 fragment to bind and bundle microtubules in vitro. In intact cells, MAP4 was required for the stabilization of microtubules induced by septin depletion. Moreover, septin depletion increased the number of cells with abnormal nuclei, and this effect was blocked by gene silencing of MAP4. These data identify a novel molecular function for septins in mammalian cells: the modulation of microtubule dynamics through interaction with MAP4.

Abbreviations used: AD, affinity domain; MAP4, microtubule-associated protein 4; MT, microtubule; PRD, proline-rich domain; ROI, region of interest.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Ian G. Macara (igm9c{at}virginia.edu).

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