Mutant IP$ {3}$ receptors attenuate store-operated Ca$^{2 }$ entry by destabilizing STIM-Orai interactions in $ extit{Drosophila}$ neuronsReport as inadecuate


Mutant IP$ {3}$ receptors attenuate store-operated Ca$^{2 }$ entry by destabilizing STIM-Orai interactions in $	extit{Drosophila}$ neurons


Mutant IP$ {3}$ receptors attenuate store-operated Ca$^{2 }$ entry by destabilizing STIM-Orai interactions in $ extit{Drosophila}$ neurons - Download this document for free, or read online. Document in PDF available to download.

Publication Date: 2016-10-15

Journal Title: Journal of Cell Science

Publisher: The Company of Biologists

Volume: 129

Pages: 3903-3910

Language: English

Type: Article

This Version: VoR

Metadata: Show full item record

Citation: Chakraborty, S., Deb, B. K., Chorna, T., Konieczny, V., Taylor, C. W., & Hasan, G. (2016). Mutant IP$_{3}$ receptors attenuate store-operated Ca$^{2+}$ entry by destabilizing STIM-Orai interactions in $\textit{Drosophila}$ neurons. Journal of Cell Science, 129 3903-3910. https://doi.org/10.1242/jcs.191585

Description: This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/jcs.191585

Abstract: Store-operated Ca$^{2+}$ entry (SOCE) occurs when loss of Ca$^{2+}$ from the endoplasmic reticulum (ER) stimulates the Ca$^{2+}$ sensor, STIM, to cluster and activate the plasma membrane Ca$^{2+}$ channel Orai (encoded by $\textit{Olf186-F}$ in flies). Inositol 1,4,5-trisphosphate receptors (IP$_{3}$Rs, which are encoded by a single gene in flies) are assumed to regulate SOCE solely by mediating ER Ca$^{2+}$ release. We show that in $\textit{Drosophila}$ neurons, mutant IP$_{3}$R attenuates SOCE evoked by depleting Ca$^{2+}$ stores with thapsigargin. In normal neurons, store depletion caused STIM and the IP$_{3}$R to accumulate near the plasma membrane, association of STIM with Orai, clustering of STIM and Orai at ER–plasma-membrane junctions and activation of SOCE. These responses were attenuated in neurons with mutant IP3Rs and were rescued by overexpression of STIM with Orai. We conclude that, after depletion of Ca$^{2+}$ stores in $\textit{Drosophila}$, translocation of the IP$_{3}$R to ER–plasma-membrane junctions facilitates the coupling of STIM to Orai that leads to activation of SOCE.

Keywords: Ca$^{2+}$ signalling, $\textit{Drosophila}$, IP$_{3}$R receptor, Orai, STIM, store-operated Ca$^{2+}$ entry

Sponsorship: The work was supported by funding from National Centre for Biological Sciences, India to G.H.; Department of Science and Technology, Ministry of Science and Technology, India to G.H.; and by the Wellcome Trust [grant number 101844 to C.W.T.]. S.C. and B.K.D. were supported by Council of Scientific and Industrial Research, India (CSIR) fellowships. Deposited in PMC for immediate release.

Embargo Lift Date: 2100-01-01

Identifiers:

External DOI: https://doi.org/10.1242/jcs.191585

This record's URL: https://www.repository.cam.ac.uk/handle/1810/260899



Rights: Attribution 4.0 International

Licence URL: http://creativecommons.org/licenses/by/4.0/





Author: Chakraborty, SumitaDeb, Bipan K. Chorna, TetyanaKonieczny, Vera Taylor, Colin W.Hasan, Gaiti

Source: https://www.repository.cam.ac.uk/handle/1810/260899



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