Cellular and Molecular Life Sciences

, Volume 71, Issue 11, pp 2165–2178 | Cite as

Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli

  • Xingjian Jin
  • Ashraf M. Mohieldin
  • Brian S. Muntean
  • Jill A. Green
  • Jagesh V. Shah
  • Kirk Mykytyn
  • Surya M. NauliEmail author
Research Article


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.


Chemosensing Ciliopathy Mechanosensing Microscope Microwire Polycystic kidney 



The authors thank Charisse Montgomery for comments regarding this manuscript. X. Jin’s work partially fulfilled the requirements for a PhD degree in Pharmacology. This work was supported by National Institute of Health, R01DK080640 (SMN) and R01GM083120 (KM). AMM is supported by F31DK096870.

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Xingjian Jin
    • 1
  • Ashraf M. Mohieldin
    • 2
  • Brian S. Muntean
    • 2
  • Jill A. Green
    • 3
  • Jagesh V. Shah
    • 4
  • Kirk Mykytyn
    • 3
  • Surya M. Nauli
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of Medicine, College of MedicineThe University of ToledoToledoUSA
  2. 2.Department of Pharmacology, College of Pharmacy and Pharmaceutical SciencesThe University of ToledoToledoUSA
  3. 3.Department of Pharmacology, College of MedicineThe Ohio State UniversityColumbusUSA
  4. 4.Department of Systems Biology, Harvard Medical School and Renal DivisionBrigham and Women’s HospitalBostonUSA
  5. 5.Department of Pharmacology, MS 1015, Health Education Building, Room 282DThe University of ToledoToledoUSA

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