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Science 329 (5990): 436-439

Copyright © 2010 by the American Association for the Advancement of Science

A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution

Qicong Hu,1 Ljiljana Milenkovic,2,3 Hua Jin,4 Matthew P. Scott,2,3,5–,8 Maxence V. Nachury,4 Elias T. Spiliotis,9,* W. James Nelson1,4,*

Abstract: In animal cells, the primary cilium transduces extracellular signals through signaling receptors localized in the ciliary membrane, but how these ciliary membrane proteins are retained in the cilium is unknown. We found that ciliary membrane proteins were highly mobile, but their diffusion was impeded at the base of the cilium by a diffusion barrier. Septin 2 (SEPT2), a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane. SEPT2 depletion resulted in loss of ciliary membrane protein localization and Sonic hedgehog signal transduction, and inhibited ciliogenesis. Thus, SEPT2 is part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium.

1 Department of Biology, Stanford University, Stanford, CA 94305, USA.
2 Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
3 Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
4 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
5 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
6 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
7 Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
8 Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
9 Department of Biology, Drexel University, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: wjnelson{at}stanford.edu (W.J.N.); ets33{at}drexel.edu (E.T.S.)

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