Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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} (W.J.N.); ets33{at} (E.T.S.)

Sept6 Is Required for Ciliogenesis in Kupffer's Vesicle, the Pronephros, and the Neural Tube during Early Embryonic Development.
G. Zhai, Q. Gu, J. He, Q. Lou, X. Chen, X. Jin, E. Bi, and Z. Yin (2014)
Mol. Cell. Biol. 34, 1310-1321
   Abstract »    Full Text »    PDF »
sept7b is essential for pronephric function and development of left-right asymmetry in zebrafish embryogenesis.
S. N. Dash, E. Lehtonen, A. A. Wasik, A. Schepis, J. Paavola, P. Panula, W. J. Nelson, and S. Lehtonen (2014)
J. Cell Sci. 127, 1476-1486
   Abstract »    Full Text »    PDF »
The fate of the primary cilium during myofibroblast transition.
M. Rozycki, M. Lodyga, J. Lam, M. Z. Miranda, K. Fatyol, P. Speight, and A. Kapus (2014)
Mol. Biol. Cell 25, 643-657
   Abstract »    Full Text »    PDF »
Role of Endothelial Cell Septin 7 in the Endocytosis of Candida albicans.
Q. T. Phan, D. K. Eng, S. Mostowy, H. Park, P. Cossart, and S. G. Filler (2013)
mBio 4, e00542-13
   Abstract »    Full Text »    PDF »
An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier.
D. K. Breslow, E. F. Koslover, F. Seydel, A. J. Spakowitz, and M. V. Nachury (2013)
J. Cell Biol. 203, 129-147
   Abstract »    Full Text »    PDF »
Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans.
M. Wojtyniak, A. G. Brear, D. M. O'Halloran, and P. Sengupta (2013)
J. Cell Sci. 126, 4381-4395
   Abstract »    Full Text »    PDF »
Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors.
F. Ye, D. K. Breslow, E. F. Koslover, A. J. Spakowitz, W. J. Nelson, and M. V. Nachury (2013)
eLife Sci 2, e00654
   Abstract »    Full Text »    PDF »
KHARON1 Mediates Flagellar Targeting of a Glucose Transporter in Leishmania mexicana and Is Critical for Viability of Infectious Intracellular Amastigotes.
K. D. Tran, D. Rodriguez-Contreras, D. P. Vieira, P. A. Yates, L. David, W. Beatty, J. Elferich, and S. M. Landfear (2013)
J. Biol. Chem. 288, 22721-22733
   Abstract »    Full Text »    PDF »
Septins 2, 7 and 9 and MAP4 colocalize along the axoneme in the primary cilium and control ciliary length.
R. Ghossoub, Q. Hu, M. Failler, M.-C. Rouyez, B. Spitzbarth, S. Mostowy, U. Wolfrum, S. Saunier, P. Cossart, W. James Nelson, et al. (2013)
J. Cell Sci. 126, 2583-2594
   Abstract »    Full Text »    PDF »
The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content.
J. R. Schaub and T. Stearns (2013)
Mol. Biol. Cell 24, 453-464
   Abstract »    Full Text »    PDF »
Centriole distal appendages promote membrane docking, leading to cilia initiation.
B. E. Tanos, H.-J. Yang, R. Soni, W.-J. Wang, F. P. Macaluso, J. M. Asara, and M.-F. B. Tsou (2013)
Genes & Dev. 27, 163-168
   Abstract »    Full Text »    PDF »
The Arf GAP ASAP1 provides a platform to regulate Arf4- and Rab11-Rab8-mediated ciliary receptor targeting.
J. Wang, Y. Morita, J. Mazelova, and D. Deretic (2012)
EMBO J. 31, 4057-4071
   Abstract »    Full Text »    PDF »
VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis.
V. Takiar, K. Mistry, M. Carmosino, N. Schaeren-Wiemers, and M. J. Caplan (2012)
Am J Physiol Cell Physiol 303, C862-C871
   Abstract »    Full Text »    PDF »
Uncovering Principles That Control Septin-Septin Interactions.
M. S. Kim, C. D. Froese, H. Xie, and W. S. Trimble (2012)
J. Biol. Chem. 287, 30406-30413
   Abstract »    Full Text »    PDF »
A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth.
A. Vernay, S. Schaub, I. Guillas, M. Bassilana, and R. A. Arkowitz (2012)
J. Cell Biol. 198, 711-730
   Abstract »    Full Text »    PDF »
The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization.
J. F. Reiter, O. E. Blacque, and M. R. Leroux (2012)
EMBO Rep. 13, 608-618
   Abstract »    Full Text »    PDF »
The future of ciliary and flagellar membrane research.
R. A. Bloodgood (2012)
Mol. Biol. Cell 23, 2407-2411
   Abstract »    Full Text »    PDF »
Scoring a backstage pass: Mechanisms of ciliogenesis and ciliary access.
F. R. Garcia-Gonzalo and J. F. Reiter (2012)
J. Cell Biol. 197, 697-709
   Abstract »    Full Text »    PDF »
Molecular Pathways: The Role of Primary Cilia in Cancer Progression and Therapeutics with a Focus on Hedgehog Signaling.
N. B. Hassounah, T. A. Bunch, and K. M. McDermott (2012)
Clin. Cancer Res. 18, 2429-2435
   Abstract »    Full Text »    PDF »
Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation.
M. Arizono, H. Bannai, K. Nakamura, F. Niwa, M. Enomoto, T. Matsu-ura, A. Miyamoto, M. W. Sherwood, T. Nakamura, and K. Mikoshiba (2012)
Science Signaling 5, ra27
   Abstract »    Full Text »    PDF »
Lipid Polarity Is Maintained in Absence of Tight Junctions.
J. Ikenouchi, M. Suzuki, K. Umeda, K. Ikeda, R. Taguchi, T. Kobayashi, S. B. Sato, T. Kobayashi, D. B. Stolz, and M. Umeda (2012)
J. Biol. Chem. 287, 9525-9533
   Abstract »    Full Text »    PDF »
The septin cytoskeleton facilitates membrane retraction during motility and blebbing.
J. K. Gilden, S. Peck, Y.-C. M. Chen, and M. F. Krummel (2012)
J. Cell Biol. 196, 103-114
   Abstract »    Full Text »    PDF »
Steric volume exclusion sets soluble protein concentrations in photoreceptor sensory cilia.
M. Najafi, N. A. Maza, and P. D. Calvert (2012)
PNAS 109, 203-208
   Abstract »    Full Text »    PDF »
Ouabain modulates ciliogenesis in epithelial cells.
I. Larre, A. Castillo, C. Flores-Maldonado, R. G. Contreras, I. Galvan, J. Munoz-Estrada, and M. Cereijido (2011)
PNAS 108, 20591-20596
   Abstract »    Full Text »    PDF »
Septins at a glance.
N. Beise and W. Trimble (2011)
J. Cell Sci. 124, 4141-4146
   Full Text »    PDF »
Subunit-dependent modulation of septin assembly: Budding yeast septin Shs1 promotes ring and gauze formation.
G. Garcia III, A. Bertin, Z. Li, Y. Song, M. A. McMurray, J. Thorner, and E. Nogales (2011)
J. Cell Biol. 195, 993-1004
   Abstract »    Full Text »    PDF »
Microtubules support a disk-like septin arrangement at the plasma membrane of mammalian cells.
M. E. Sellin, P. Holmfeldt, S. Stenmark, and M. Gullberg (2011)
Mol. Biol. Cell 22, 4588-4601
   Abstract »    Full Text »    PDF »
Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins.
C. E. Larkins, G. D. G. Aviles, M. P. East, R. A. Kahn, and T. Caspary (2011)
Mol. Biol. Cell 22, 4694-4703
   Abstract »    Full Text »    PDF »
The emerging functions of septins in metazoans.
J. Saarikangas and Y. Barral (2011)
EMBO Rep. 12, 1118-1126
   Abstract »    Full Text »    PDF »
Scrutinizing ciliopathies by unraveling ciliary interaction networks.
J. van Reeuwijk, H. H. Arts, and R. Roepman (2011)
Hum. Mol. Genet. 20, R149-R157
   Abstract »    Full Text »    PDF »
Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei.
M. Oberholzer, G. Langousis, H. T. Nguyen, E. A. Saada, M. M. Shimogawa, Z. O. Jonsson, S. M. Nguyen, J. A. Wohlschlegel, and K. L. Hill (2011)
Mol. Cell. Proteomics 10, M111.010538
   Abstract »    Full Text »    PDF »
Deciphering the rules governing assembly order of mammalian septin complexes.
M. E. Sellin, L. Sandblad, S. Stenmark, and M. Gullberg (2011)
Mol. Biol. Cell 22, 3152-3164
   Abstract »    Full Text »    PDF »
Evolution: Tracing the origins of centrioles, cilia, and flagella.
Z. Carvalho-Santos, J. Azimzadeh, J. B. Pereira-Leal, and M. Bettencourt-Dias (2011)
J. Cell Biol. 194, 165-175
   Abstract »    Full Text »    PDF »
Loss of Bardet-Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting.
A. L. D. Tadenev, H. M. Kulaga, H. L. May-Simera, M. W. Kelley, N. Katsanis, and R. R. Reed (2011)
PNAS 108, 10320-10325
   Abstract »    Full Text »    PDF »
Septin filaments exhibit a dynamic, paired organization that is conserved from yeast to mammals.
B. S. DeMay, X. Bai, L. Howard, P. Occhipinti, R. A. Meseroll, E. T. Spiliotis, R. Oldenbourg, and A. S. Gladfelter (2011)
J. Cell Biol. 193, 1065-1081
   Abstract »    Full Text »    PDF »
Life's demons: information and order in biology: What subcellular machines gather and process the information necessary to sustain life?.
P. M. Binder and A. Danchin (2011)
EMBO Rep. 12, 495-499
   Full Text »    PDF »
A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells.
S. S. Francis, J. Sfakianos, B. Lo, and I. Mellman (2011)
J. Cell Biol. 193, 219-233
   Abstract »    Full Text »    PDF »
Sonic Hedgehog-induced Proliferation Requires Specific Gα Inhibitory Proteins.
M. Barzi, D. Kostrz, A. Menendez, and S. Pons (2011)
J. Biol. Chem. 286, 8067-8074
   Abstract »    Full Text »    PDF »
Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia.
J. B. Wallingford and B. Mitchell (2011)
Genes & Dev. 25, 201-213
   Abstract »    Full Text »    PDF »
Cilia 2010: The Surprise Organelle of the Decade.
E. F. Smith and R. Rohatgi (2011)
Science Signaling 4, mr1
   Abstract »    Full Text »    PDF »
Septins at the Nexus.
Y. Barral (2010)
Science 329, 1289-1290
   Abstract »    Full Text »    PDF »
Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis.
S. K. Kim, A. Shindo, T. J. Park, E. C. Oh, S. Ghosh, R. S. Gray, R. A. Lewis, C. A. Johnson, T. Attie-Bittach, N. Katsanis, et al. (2010)
Science 329, 1337-1340
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882