Next Article in Journal
miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis
Next Article in Special Issue
Role of the TRPV Channels in the Endoplasmic Reticulum Calcium Homeostasis
Previous Article in Journal
Modulation of Cell–Cell Interactions in Drosophila Oocyte Development
Previous Article in Special Issue
STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons
Open AccessArticle

Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells

1
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China
2
Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, ON N1G 2W1, Canada
3
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China
4
Central Institute for Experimental Animals, Kawasaki, Kanagawa 210-0821, Japan
5
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(2), 275; https://doi.org/10.3390/cells9020275
Received: 14 November 2019 / Revised: 11 January 2020 / Accepted: 20 January 2020 / Published: 22 January 2020
(This article belongs to the Special Issue Organellar Calcium Signaling in Physiology and Pathophysiology)
Being the largest the Ca2+ store in mammalian cells, endoplasmic reticulum (ER)-mediated Ca2+ signalling often involves both Ca2+ release via inositol 1, 4, 5-trisphosphate receptors (IP3R) and store operated Ca2+ entries (SOCE) through Ca2+ release activated Ca2+ (CRAC) channels on plasma membrane (PM). IP3Rs are functionally coupled with CRAC channels and other Ca2+ handling proteins. However, it still remains less well defined as to whether IP3Rs could regulate ER-mediated Ca2+ signals independent of their Ca2+ releasing ability. To address this, we generated IP3Rs triple and double knockout human embryonic kidney (HEK) cell lines (IP3Rs-TKO, IP3Rs-DKO), and systemically examined ER Ca2+ dynamics and CRAC channel activity in these cells. The results showed that the rate of ER Ca2+ leakage and refilling, as well as SOCE were all significantly reduced in IP3Rs-TKO cells. And these TKO effects could be rescued by over-expression of IP3R3. Further, results showed that the diminished SOCE was caused by NEDD4L-mediated ubiquitination of Orai1 protein. Together, our findings indicate that IP3R3 is one crucial player in coordinating ER-mediated Ca2+ signalling. View Full-Text
Keywords: IP3R; store-operated Ca2+ entry; Orai1; SERCA; NEDD4L; calcium IP3R; store-operated Ca2+ entry; Orai1; SERCA; NEDD4L; calcium
Show Figures

Figure 1

MDPI and ACS Style

Yue, L.; Wang, L.; Du, Y.; Zhang, W.; Hamada, K.; Matsumoto, Y.; Jin, X.; Zhou, Y.; Mikoshiba, K.; Gill, D.L.; Han, S.; Wang, Y. Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells. Cells 2020, 9, 275. https://doi.org/10.3390/cells9020275

AMA Style

Yue L, Wang L, Du Y, Zhang W, Hamada K, Matsumoto Y, Jin X, Zhou Y, Mikoshiba K, Gill DL, Han S, Wang Y. Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells. Cells. 2020; 9(2):275. https://doi.org/10.3390/cells9020275

Chicago/Turabian Style

Yue, Lili; Wang, Liuqing; Du, Yangchun; Zhang, Wei; Hamada, Kozo; Matsumoto, Yoshifumi; Jin, Xi; Zhou, Yandong; Mikoshiba, Katsuhiko; Gill, Donald L.; Han, Shengcheng; Wang, Youjun. 2020. "Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells" Cells 9, no. 2: 275. https://doi.org/10.3390/cells9020275

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop