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Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli
Open accessAbstract
Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP3 receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell.
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“Upon activation, ciliary V2R seems to activate adenylyl cyclase, which increases local cAMP concentrations and activates a cation-selective channel to regulate intraciliary Ca+2 signals 162.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [162]
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“Type 2 vasopressin receptor (V2R) which regulates Na+ and water reabsorption in the mammalian nephron has also been reported to localize to cilia on renal epithelial cells 162.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [162]
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Citations
Cites
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Self-citationPrimary cilia are not calcium-responsive mechanosensors
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Primary cilium-dependent signaling mechanisms
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Self-citationIntraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry
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Metadata
- Authors
- Jin, X., Mohieldin, A. M., Muntean, B. S., Green, J. A., Shah, J. V., Mykytyn, K., & Nauli, S. M.
- Affiliations
- University of Toledo (US)
- The Ohio State University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Nauli, Surya M.
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2013-10-09
- Volume
- 71
- Issue
- 11
- Pages
- 2165-2178
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC3981964
- OpenAlex
- W2135672728
- Cited by
- 137
- References
- 26
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 14 · 2018: 7 · 2017: 14 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 2
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM083120)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080640, F31DK096870)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- primary cilia, calcium signaling, fluid shear stress, polycystin-2, Cav1.2, ryanodine receptor, IP3 receptor, thrombin, calcium ionophore, single-cell imaging
- MeSH terms
- Animals, Cilia, Cytoplasm, Epithelial Cells, Gene Expression Regulation, Kidney, Rheology, Stress, Mechanical, Swine, Thrombin, Ryanodine Receptor Calcium Release Channel, Calcium Signaling, Calcium Channels, L-Type, Mechanotransduction, Cellular, TRPP Cation Channels, Receptors, TNF-Related Apoptosis-Inducing Ligand, Inositol 1,4,5-Trisphosphate Receptors, Molecular Imaging, Single-Cell Analysis, Calcium Ionophores, Primary Cell Culture
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