title: Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel.
abstract: AK032317 is the GenBank accession no. of a full-length RIKEN mouse cDNA. It encodes a putative variant of the C3-type TRPC (transient receptor potential channel) that differs from the previously cloned murine TRPC3 cDNA in that it has a 5' extension stemming from inclusion of an additional exon (exon 0). The extended cDNA adds 62 aa to the sequence of the murine TRPC3. Here, we report the cloning of a cDNA encoding the human homologue of this extended TRPC3 having a highly homologous 73-aa N-terminal extension, referred to as hTRPC3a. A query of the GenBank genomic database predicts the existence of a similar gene product also in rats. Transient expression of the longer TRPC3a in human embryonic kidney (HEK) cells showed that it mediates Ca2+ entry in response to stimulation of the Gq-phospholipase C beta pathway, which is similar to that mediated by the shorter hTRPC3. However, after isolation of HEK cells expressing hTRPC3 in stable form, TRPC3a gave rise to Ca2+-entry channels that are not only activated by the Gq-phospholipase C beta pathway (receptor-activated Ca entry) but also by thapsigargin triggered store depletion. In conjunction with findings from our and other laboratories that TRPC1, TRPC2, TRPC4, TRPC5, and TRPC7, can each mediate store-depletion-activated Ca2+ entry in mammalian cells, our findings with hTRC3a support our previous proposal that TRPCs form capacitative Ca-entry channels.
authors.affiliation: Transmembrane Signaling Group, Laboratory of Signal Transduction, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Eda
authors.initials: E
authors.lastname: Yildirim
authors.forename: Brian T
authors.initials: BT
authors.lastname: Kawasaki
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D018076:DNA, Complementary; D007473:Ion Channels; D020033:Protein Isoforms; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D019284:Thapsigargin
references.citation: J Cell Biol. 1997 Sep 22;138(6):1333-41
references.pmid: 9298988
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15195-202
references.pmid: 8986787
references.citation: J Biol Chem. 1998 Jan 2;273(1):133-42
references.pmid: 9417057
references.citation: EMBO J. 1998 Aug 3;17(15):4274-82
references.pmid: 9687496
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2060-4
references.pmid: 10051594
references.citation: J Physiol. 1999 Jul 15;518 Pt 2:345-58
references.pmid: 10381584
references.citation: Am J Physiol Cell Physiol. 2004 Dec;287(6):C1709-16
references.pmid: 15342342
references.citation: Nat Cell Biol. 2001 May;3(5):499-502
references.pmid: 11331878
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14955-60
references.pmid: 10611319
references.citation: J Biol Chem. 2000 Feb 4;275(5):3403-11
references.pmid: 10652333
references.citation: J Biol Chem. 2000 Dec 15;275(50):39055-60
references.pmid: 10984475
references.citation: FEBS Lett. 2001 Jan 5;487(3):377-83
references.pmid: 11163362
references.citation: Nat Cell Biol. 2001 Feb;3(2):121-7
references.pmid: 11175743
references.citation: Nature. 2001 Apr 5;410(6829):705-9
references.pmid: 11287959
references.citation: Cell. 2002 Mar 8;108(5):595-8
references.pmid: 11893331
references.citation: J Biol Chem. 2002 Apr 5;277(14):12302-9
references.pmid: 11805119
references.citation: J Biol Chem. 2002 Jul 26;277(30):26950-8
references.pmid: 12011062
references.citation: Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):95-104
references.pmid: 12531519
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2220-5
references.pmid: 12601176
references.citation: J Biol Chem. 2003 Jun 13;278(24):21649-54
references.pmid: 12686562
references.citation: Mol Cell. 2004 Aug 27;15(4):635-46
references.pmid: 15327778
references.citation: Nature. 1988 Sep 22;335(6188):355-8
references.pmid: 2843772
references.citation: Nature. 1989 Jun 8;339(6224):439-45
references.pmid: 2725677
references.citation: J Biol Chem. 1990 Jul 5;265(19):11273-84
references.pmid: 2162842
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10798-802
references.pmid: 8248173
references.citation: FEBS Lett. 1995 Oct 16;373(3):193-8
references.pmid: 7589464
references.citation: Cell. 1996 May 31;85(5):661-71
references.pmid: 8646775
references.citation: Biochem J. 1996 Mar 1;314 ( Pt 2):710-1
references.pmid: 8670090
references.citation: Neuron. 1996 Jun;16(6):1189-96
references.pmid: 8663995
references.citation: EMBO J. 1996 Nov 15;15(22):6166-71
references.pmid: 8947038
references.citation: Biochem Biophys Res Commun. 1997 Nov 7;240(1):167-72
references.pmid: 9367904