title: Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry.
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 RTN4 in cellular Ca(2+) homeostasis.
authors.affiliation: From the Vascular Biology and Therapeutics Program, Department of Pharmacology.
authors.forename: Levente
authors.initials: L
authors.lastname: Jozsef
authors.forename: Keitaro
authors.initials: K
authors.lastname: Tashiro
authors.forename: Andrew
authors.initials: A
authors.lastname: Kuo
authors.forename: Eon Joo
authors.initials: EJ
authors.lastname: Park
authors.forename: Athanasia
authors.initials: A
authors.lastname: Skoura
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.forename: Felix
authors.initials: F
authors.lastname: Rivera-Molina
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Harrison
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Iwakiri
authors.forename: Derek
authors.initials: D
authors.lastname: Toomre
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D006706:Homeostasis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000070816:Nogo Receptor 1; D000071740:ORAI1 Protein; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: Apoptosis; Cell Signaling; Endoplasmic Reticulum (ER); Imaging; Membrane; reticulons