title: Choline transporter-like protein 4 (CTL4) links to non-neuronal acetylcholine synthesis.
abstract: Synthesis of acetylcholine (ACh) by non-neuronal cells is now well established and plays diverse physiologic roles. In neurons, the Na(+) -dependent, high affinity choline transporter (CHT1) is absolutely required for ACh synthesis. In contrast, some non-neuronal cells synthesize ACh in the absence of CHT1 indicating a fundamental difference in ACh synthesis compared to neurons. The aim of this study was to identify choline transporters, other than CHT1, that play a role in non-neuronal ACh synthesis. ACh synthesis was studied in lung and colon cancer cell lines focusing on the choline transporter-like proteins, a five gene family choline-transporter like protein (CTL)1-5. Supporting a role for CTLs in choline transport in lung cancer cells, choline transport was Na(+) -independent and CTL1-5 were expressed in all cells examined. CTL1, 2, and 5 were expressed at highest levels and knockdown of CTL1, 2, and 5 decreased choline transport in H82 lung cancer cells. Knockdowns of CTL1, 2, 3, and 5 had no effect on ACh synthesis in H82 cells. In contrast, knockdown of CTL4 significantly decreased ACh secretion by both lung and colon cancer cells. Conversely, increasing expression of CTL4 increased ACh secretion. These results indicate that CTL4 mediates ACh synthesis in non-neuronal cell lines and presents a mechanism to target non-neuronal ACh synthesis without affecting neuronal ACh synthesis.
authors: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
authors: Pingfang
authors: P
authors: Song
authors: Stephen S
authors: SS
authors: Rekow
authors: Corey-Ayne
authors: CA
authors: Singleton
authors: Harmanjatinder S
authors: HS
authors: Sekhon
authors: Gregory A
authors: GA
authors: Dissen
authors: Minerva
authors: M
authors: Zhou
authors: Barbara
authors: B
authors: Campling
authors: Jon
authors: J
authors: Lindstrom
authors: Eliot R
authors: ER
authors: Spindel
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis* / Q000378:metabolism; D001285:Atropine / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002794:Choline / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms; D003470:Culture Media / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D055752:Small Cell Lung Carcinoma; D014316:Tritium
chemical_list: D003470:Culture Media; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists; D034741:RNA, Small Interfering; C583905:SLC44A4 protein, human; D014316:Tritium; D001285:Atropine; D002794:Choline; D000109:Acetylcholine
keywords: CTL; acetylcholine; choline; choline transporter; choline transporter-like protein; lung cancer
references: Am J Respir Cell Mol Biol. 2003 Apr;28(4):473-7
references: 12654636
references: Nat Med. 2010 Jan;16(1):45-8
references: 20037594
references: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17397-402
references: 20852067
references: J Cell Biochem. 2003 Oct 15;90(3):525-33
references: 14523987
references: Pharmacol Ther. 2000 Apr;86(1):29-48
references: 10760545
references: Eur Urol. 2007 Apr;51(4):1042-53
references: 17084519
references: Biochem Biophys Res Commun. 2000 Oct 5;276(3):862-7
references: 11027560
references: Neurochem Int. 2011 Feb;58(3):354-65
references: 21185344
references: Arch Biochem Biophys. 2009 May 1;485(1):88-96
references: 19236841
references: Cancer Res. 2003 Jan 1;63(1):214-21
references: 12517800
references: Cancer Res. 2007 Apr 15;67(8):3936-44
references: 17440109
references: Cancer Res. 2008 Jun 15;68(12):4693-700
references: 18559515
references: Cancer. 1992 Apr 15;69(8):2064-74
references: 1311980
references: Mol Pharm. 2006 Sep-Oct;3(5):496-506
references: 17009848
references: Cell Tissue Res. 2009 Nov;338(2):203-15
references: 19820967
references: Horm Metab Res. 2007 Feb;39(2):125-35
references: 17326008
references: Gastroenterology. 1996 Aug;111(2):401-8
references: 8690205
references: Am J Physiol Gastrointest Liver Physiol. 2008 Sep;295(3):G591-7
references: 18653726
references: Ann Anat. 2005 Nov;187(5-6):521-8
references: 16320831
references: J Neurosci. 2012 Apr 18;32(16):5573-84
references: 22514319
references: Naunyn Schmiedebergs Arch Pharmacol. 1997 Apr;355(4):515-23
references: 9109369
references: Nat Neurosci. 2000 Feb;3(2):120-5
references: 10649566
references: J Pharmacol Sci. 2009 Jan;109(1):102-9
references: 19122366
references: Neurochem Res. 2007 Nov;32(11):1833-42
references: 17520363
references: Naunyn Schmiedebergs Arch Pharmacol. 1997 Nov;356(5):694-7
references: 9402051
references: Brain Res. 1989 Apr 10;484(1-2):217-27
references: 2713682
references: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8762-7
references: 15173594
references: Methods. 2009 Sep;49(1):70-7
references: 19559089
references: J Physiol. 2011 Feb 15;589(Pt 4):953-62
references: 21135046
references: Biochim Biophys Acta. 2012 Mar;1818(3):559-65
references: 22206629
references: Endocrinology. 2004 May;145(5):2498-506
references: 14764638
references: Br J Pharmacol. 2012 Jun;166(4):1388-402
references: 22300281
references: J Neurochem. 2005 Mar;92(5):1116-25
references: 15715662
references: Biol Pharm Bull. 2010;33(4):691-6
references: 20410607
references: Scand J Gastroenterol. 2011 Apr;46(4):446-55
references: 21265716
references: J Pharmacol Sci. 2008 Feb;106(2):180-5
references: 18285655
references: J Neurochem. 2005 Sep;94(5):1427-37
references: 16000150
references: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1835-40
references: 10677542
references: Am J Physiol. 1994 Nov;267(5 Pt 1):C1279-87
references: 7977691
references: Br J Pharmacol. 2008 Aug;154(8):1558-71
references: 18500366
references: J Neurochem. 2006 Apr;97(1):1-12
references: 16524384
references: J Neurochem. 2009 Aug;110(4):1297-309
references: 19519661