title: TRUSS, TNF-R1, and TRPC ion channels synergistically reverse endoplasmic reticulum Ca2+ storage reduction in response to m1 muscarinic acetylcholine receptor signaling.
abstract: Although most signaling responses initiated by tumor necrosis factor-alpha (TNF-alpha) occur in a Ca(2+)-independent fashion, TNF-alpha receptor signaling augments Ca(2+) entry induced by Galpha(q/11) G-protein coupled receptors (GPCRs) in endothelial cells and increases trans-endothelial permeability. The signaling events involved in GPCR-induced Ca(2+) influx have been characterized and involve store-operated Ca(2+) entry facilitated by the Ca(2+) permeable ion channel, transient receptor potential canonical 4 (TRPC4). Little is known about the mechanisms by which TNF-alpha receptor signaling augments GPCR-induced Ca(2+) entry. TNF-alpha Receptor Ubiquitous Signaling and Scaffolding protein (TRUSS) is a tumor necrosis factor receptor-1 (TNF-R1)-associated protein whose gene name is TRPC4-associated protein (TRPC4AP). The goal of our study was to test the hypothesis that TRUSS serves to link TNF-R1 and GPCR-signaling pathways at the level of TRPC4 by: (i) determining if TRUSS and TNF-R1 interact with TRPC4, and (ii) investigating the role of TRUSS, TNF-R1, and TRPC4 in GPCR-induced Ca(2+) signaling. Here, we show that TRUSS and TNF-R1 interact with a sub-family of TRPC channels (TRPC1, 4, and 5). In addition, we show that TRUSS and TNF-R1 function together with TRPC4 to elevate endoplasmic reticulum Ca(2+) filling in the context of reduced endoplasmic reticulum Ca(2+) storage initiated by G-protein coupled m1 muscarinic acetylcholine receptor (m1AchR) signaling. Together, these findings suggest that TNF-R1, TRUSS, and TRPC4 augment Ca(2+) loading of endoplasmic reticulum Ca(2+) stores in the context of m1AchR stimulation and provide new insights into the mechanisms that connect TNF-R1 to GPCR-induced Ca(2+) signaling.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Mace
authors.forename: Marc P
authors.initials: MP
authors.lastname: Lussier
authors.forename: Guylain
authors.initials: G
authors.lastname: Boulay
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Terry-Powers
authors.forename: Helen
authors.initials: H
authors.lastname: Parfrey
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Perraud
authors.forename: David W H
authors.initials: DW
authors.lastname: Riches
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D010539:Permeability; D043643:Receptor, Muscarinic M1 / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D043643:Receptor, Muscarinic M1; D047888:Receptors, Tumor Necrosis Factor, Type I; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; C550321:TRPC4AP protein, human; D002118:Calcium
references.citation: Cell Signal. 2007 Jul;19(7):1457-64
references.pmid: 17321109
references.citation: Cell Calcium. 2007 Aug;42(2):205-11
references.pmid: 17517433
references.citation: Nat Cell Biol. 2001 Feb;3(2):121-7
references.pmid: 11175743
references.citation: Science. 2002 May 31;296(5573):1634-5
references.pmid: 12040173
references.citation: J Cell Biol. 2007 Aug 27;178(5):829-41
references.pmid: 17724122
references.citation: Mol Cell Biol. 2003 Nov;23(22):8334-44
references.pmid: 14585990
references.citation: J Cell Biol. 2005 May 9;169(3):435-45
references.pmid: 15866891
references.citation: Cell Calcium. 1996 Sep;20(3):235-42
references.pmid: 8894270
references.citation: Cell Calcium. 2007 Aug;42(2):103-10
references.pmid: 17349691
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17542-7
references.pmid: 17956991
references.citation: Surgery. 2009 Aug;146(2):198-205
references.pmid: 19628074
references.citation: Neurosci Lett. 2009 Feb 6;450(3):344-6
references.pmid: 19059308
references.citation: Pharmacol Ther. 2008 Feb;117(2):232-43
references.pmid: 18082893
references.citation: Am J Physiol Cell Physiol. 2009 Nov;297(5):C1284-93
references.pmid: 19692652
references.citation: Br J Pharmacol. 1995 Jan;114(1):4-5
references.pmid: 7712026
references.citation: Physiol Rev. 2005 Apr;85(2):757-810
references.pmid: 15788710
references.citation: Curr Mol Med. 2004 May;4(3):291-301
references.pmid: 15101686
references.citation: Am J Physiol. 1990 Jun;258(6 Pt 1):C1006-15
references.pmid: 2360617
references.citation: Cell Death Differ. 2003 Jan;10(1):45-65
references.pmid: 12655295
references.citation: FEBS Lett. 2006 Aug 21;580(19):4591-6
references.pmid: 16876162
references.citation: Pharmacology. 2000 Feb;60(2):82-9
references.pmid: 10657757
references.citation: J Biol Chem. 2005 May 13;280(19):19393-400
references.pmid: 15757897
references.citation: Cell. 2007 Dec 28;131(7):1327-39
references.pmid: 18160041
references.citation: Am J Respir Cell Mol Biol. 1996 Jul;15(1):55-63
references.pmid: 8679222
references.citation: Nature. 2006 May 11;441(7090):179-85
references.pmid: 16582901
references.citation: Science. 2006 May 26;312(5777):1220-3
references.pmid: 16645049
references.citation: Vascul Pharmacol. 2002 Nov;39(4-5):173-85
references.pmid: 12747958
references.citation: Nat Cell Biol. 2007 Jun;9(6):636-45
references.pmid: 17486119
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2598-602
references.pmid: 8464866
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):50-5
references.pmid: 18449908
references.citation: Circ Res. 2002 Jul 12;91(1):70-6
references.pmid: 12114324
references.citation: Curr Biol. 2005 Jul 12;15(13):1235-41
references.pmid: 16005298
references.citation: J Immunol. 1998 Jan 15;160(2):943-52
references.pmid: 9551933
references.citation: Nat Cell Biol. 2006 Sep;8(9):1003-10
references.pmid: 16906149
references.citation: Cell. 2001 Feb 23;104(4):487-501
references.pmid: 11239407
references.citation: Trends Neurosci. 2008 Sep;31(9):454-63
references.pmid: 18675468
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):534-8
references.pmid: 8290560
references.citation: Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):95-104
references.pmid: 12531519
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Oct;281(4):L958-68
references.pmid: 11557600
references.citation: Nature. 2005 Oct 20;437(7062):1173-8
references.pmid: 16189514
references.citation: FASEB J. 1995 Jun;9(9):788-98
references.pmid: 7601343