The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1
Open accessAbstract
Background— When challenged with extracellular fluid shear stress, vascular endothelial cells are known to release nitric oxide, an important vasodilator. Here, we show that the ability of cultured endothelial cells to sense a low range of fluid shear depends on apical membrane organelles, called cilia, and that cilia are compartments required for proper localization and function of the mechanosensitive polycystin-1 molecule. Methods and Results— Cells with the Pkd1 null/null or Tg737 orpk/orpk mutation encoded for polycystin-1 or polaris, respectively, are unable to transmit extracellular shear stress into intracellular calcium signaling and biochemical nitric oxide synthesis. Cytosolic calcium and nitric oxide recordings further show that fluid shear sensing is a cilia-specific mechanism because other mechanical or pharmacological stimulation does not abolish calcium and nitric oxide signaling in polycystin-1 and polaris mutant endothelial cells. Polycystin-1 localized in the basal body of Tg737 orpk/orpk endothelial cells is insufficient for a fluid shear stress response. Furthermore, the optimal shear stress to which the cells respond best does not alter the apical cilia structure but modifies the responsiveness of cells to higher shear stresses through proteolytic modification of polycystin-1. Conclusions— We demonstrate for the first time that polycystin-1 (required for cilia function) and polaris (required for cilia structure) are crucial mechanosensitive molecules in endothelial cells. We propose that a distinctive communication with the extracellular microenvironment depends on the proper localization and function of polycystin-1 in cilia.
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Cites
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
Nauli, S. M., Alenghat, F. J., Luo, Y., Williams, E., Vassilev, P., Li, X., Elia, A. E. H., Lu, W., Brown, E. M., Quinn, S. J., et al. (2003) · Nature Genetics · doi:10.1038/ng1076 · Cited by 2,057
Self-citationA mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima, E., Irani-Tehrani, M., Kiosses, W. B., Dejana, E., Schultz, D. A., Engelhardt, B., Cao, G., DeLisser, H., & Schwartz, M. A. (2005) · Nature · doi:10.1038/nature03952 · Cited by 1,711
The Primary Cilium as the Cell's Antenna: Signaling at a Sensory Organelle
Singla, V., & Reiter, J. F. (2006) · Science · doi:10.1126/science.1124534 · Cited by 1,189
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Overview of Structure and Function of Mammalian Cilia
Satir, P., & Christensen, S. T. (2007) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.040705.141236 · Cited by 1,142
Yoder, B. K., Hou, X., & Guay-Woodford, L. M. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000029587.47950.25 · Cited by 935
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Bending the MDCK Cell Primary Cilium Increases Intracellular Calcium
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Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse
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CENTRIOLES AND THE FORMATION OF RUDIMENTARY CILIA BY FIBROBLASTS AND SMOOTH MUSCLE CELLS
Sorokin, S. (1962) · The Journal of Cell Biology · doi:10.1083/jcb.15.2.363 · Cited by 732
Cited by
The Primary Cilium as a Complex Signaling Center
Berbari, N. F., O'Connor, A. K., Haycraft, C. J., & Yoder, B. K. (2009) · Current Biology · doi:10.1016/j.cub.2009.05.025 · Cited by 621
Davis, M. J., Earley, S., Li, Y.-S., & Chien, S. (2023) · Physiological Reviews · doi:10.1152/physrev.00053.2021 · Cited by 273
Endothelial Cilia Mediate Low Flow Sensing during Zebrafish Vascular Development
Goetz, J. G., Steed, E., Ferreira, R. R., Roth, S., Ramspacher, C., Boselli, F., Charvin, G., Liebling, M., Wyart, C., Schwab, Y., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.032 · Cited by 219
Emerging role of Toll-like receptors in atherosclerosis
Curtiss, L. K., & Tobias, P. S. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800056-jlr200 · Cited by 225
“Arterial endothelial cells possess a single cilium able to detect the mechanical forces of blood flow (18-20) that distinguish disturbed flow from laminar flow.”
Primary cilium-dependent signaling mechanisms
Pala, R., Alomari, N., & Nauli, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112272 · Cited by 205
Self-citation
Metadata
- Authors
- Nauli, S. M., Kawanabe, Y., Kaminski, J. J., Pearce, W. J., Ingber, D. E., & Zhou, J.
- Venue
- Circulation
- Published
- 2008-03-04
- Volume
- 117
- Issue
- 9
- Pages
- 1161-1171
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2150782716
- Cited by
- 466
- References
- 52
- FWCI
- 17.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Nauli, S. M., Kawanabe, Y., Kaminski, J. J., Pearce, W. J., Ingber, D. E., & Zhou, J. (2008). Endothelial Cilia Are Fluid Shear Sensors That Regulate Calcium Signaling and Nitric Oxide Production Through Polycystin-1. Circulation. https://doi.org/10.1161/circulationaha.107.710111
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