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Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry

Jozsef, Levente ; Tashiro, Keitaro ; Kuo, Andrew ; Park, Eon Joo ; Skoura, Athanasia ; Albinsson, Sebastian LU ; Rivera-Molina, Felix ; Harrison, Kenneth D ; Iwakiri, Yasuko and Toomre, Derek , et al. (2014) In Journal of Biological Chemistry 289(13). p.95-9380
Abstract

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of... (More)

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca(2+) homeostasis.

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publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Apoptosis, Calcium, Calcium Channels, Cell Line, Endoplasmic Reticulum, GPI-Linked Proteins, Gene Knockout Techniques, Homeostasis, Membrane Glycoproteins, Mice, Myelin Proteins, Receptors, Cell Surface
in
Journal of Biological Chemistry
volume
289
issue
13
pages
16 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:24558039
  • scopus:84897447156
ISSN
1083-351X
DOI
10.1074/jbc.M114.548602
language
English
LU publication?
no
id
4b4e0854-a19a-43ee-8eb1-5d8f91a7c77a
date added to LUP
2016-04-19 09:57:32
date last changed
2025-01-11 23:07:49
@article{4b4e0854-a19a-43ee-8eb1-5d8f91a7c77a,
  abstract     = {{<p>Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca(2+) homeostasis.</p>}},
  author       = {{Jozsef, Levente and Tashiro, Keitaro and Kuo, Andrew and Park, Eon Joo and Skoura, Athanasia and Albinsson, Sebastian and Rivera-Molina, Felix and Harrison, Kenneth D and Iwakiri, Yasuko and Toomre, Derek and Sessa, William C}},
  issn         = {{1083-351X}},
  keywords     = {{Animals; Apoptosis; Calcium; Calcium Channels; Cell Line; Endoplasmic Reticulum; GPI-Linked Proteins; Gene Knockout Techniques; Homeostasis; Membrane Glycoproteins; Mice; Myelin Proteins; Receptors, Cell Surface}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{13}},
  pages        = {{95--9380}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry}},
  url          = {{http://dx.doi.org/10.1074/jbc.M114.548602}},
  doi          = {{10.1074/jbc.M114.548602}},
  volume       = {{289}},
  year         = {{2014}},
}