title: Expression of 1N3R-Tau isoform inhibits cell proliferation by inducing S phase arrest in N2a cells.
abstract: Tau is a microtubule-associated protein implicated in neurodegenerative tauopathies. Six tau isoforms are generated from a single gene through alternative splicing of exons 2, 3 and 10 in human brain. Differential expression of tau isoforms has been detected in different brain areas, during neurodevelopment and in neurodegenerative disorders. However, the biological significance of different tau isoforms is not clear. Here, we investigated the individual effect of six different isoforms of tau on cell proliferation and the possible mechanisms by transient expression of eGFP-labeled tau isoform plasmid in N2a cells. Our study showed the transfection efficiency was comparable between different isoforms of tau by examining GFP expression. Compared with other isoforms, we found expression of 1N3R-tau significantly inhibited cell proliferation by Cell Counting Kit-8 assay and BrdU incorporation. Flow cytometry analysis further showed expression of 1N3R-tau induced S phase arrest. Compared with the longest isoform of tau, expression of 1N3R-tau induced cyclin E translocation from the nuclei to cytoplasm, while it did not change the level of cell cycle checkpoint proteins. These data indicate that 1N3R-tau inhibits cell proliferation through inducing S phase arrest.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gong-Ping
authors.initials: GP
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: En-Jie
authors.initials: EJ
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Da-Min
authors.initials: DM
authors.lastname: Chai
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Yao
authors.affiliation: Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus; D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival; D019927:Cyclin E / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology*; D024801:Tauopathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014162:Transfection; D016875:tau Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D019927:Cyclin E; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D016875:tau Proteins; D049452:Green Fluorescent Proteins
references.citation: FASEB J. 2007 Jul;21(9):2149-61
references.pmid: 17341679
references.citation: J Cell Physiol. 2012 Mar;227(3):1220-5
references.pmid: 21604267
references.citation: Assay Drug Dev Technol. 2011 Oct;9(5):503-13
references.pmid: 21561378
references.citation: Neurobiol Aging. 2013 Jul;34(7):1922.e7-1922.e12
references.pmid: 23428180
references.citation: Genes Brain Behav. 2008 Feb;7 Suppl 1:92-100
references.pmid: 18184373
references.citation: J Cell Sci. 2001 Mar;114(Pt 6):1179-87
references.pmid: 11228161
references.citation: Dev Biol. 1992 Nov;154(1):195-204
references.pmid: 1426626
references.citation: PLoS One. 2009;4(10):e7280
references.pmid: 19794916
references.citation: FEBS Lett. 1995 Nov 20;375(3):243-8
references.pmid: 7498509
references.citation: Hum Mol Genet. 2011 Dec 15;20(24):4947-77
references.pmid: 21949350
references.citation: FEBS Lett. 2004 Oct 8;576(1-2):183-9
references.pmid: 15474035
references.citation: Hum Mol Genet. 2012 Sep 15;21(18):4094-103
references.pmid: 22723018
references.citation: EMBO J. 1992 Nov;11(11):3953-61
references.pmid: 1396588
references.citation: Mol Biol Cell. 2002 Mar;13(3):1030-45
references.pmid: 11907280
references.citation: J Biol Chem. 2012 Jun 8;287(24):20711-9
references.pmid: 22539343
references.citation: Cytometry. 1997 Dec 1;29(4):286-91
references.pmid: 9415410
references.citation: Mol Neurodegener. 2009 May 02;4:18
references.pmid: 19409104
references.citation: PLoS One. 2013;8(12):e84849
references.pmid: 24386422
references.citation: J Comp Neurol. 2008 Dec 20;511(6):788-803
references.pmid: 18925637
references.citation: Prog Neurobiol. 2008 Jun;85(2):148-75
references.pmid: 18448228
references.citation: J Alzheimers Dis. 2013;37(4):795-808
references.pmid: 23948915
references.citation: J Neurochem. 2000 Apr;74(4):1749-57
references.pmid: 10737634
references.citation: Neurobiol Aging. 2013 Nov;34(11):2551-63
references.pmid: 23769395
references.citation: J Alzheimers Dis. 2011;23(1):161-9
references.pmid: 20966551
references.citation: Hum Mol Genet. 2001 Sep 15;10(19):2143-55
references.pmid: 11590131
references.citation: Neurochem Res. 2008 Jun;33(6):1138-44
references.pmid: 18231852
references.citation: Brain Res Brain Res Rev. 2000 Aug;33(1):95-130
references.pmid: 10967355
references.citation: Curr Aging Sci. 2008 Mar;1(1):56-61
references.pmid: 20021373
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3591-6
references.pmid: 17360687
references.citation: J Neurochem. 2006 Aug;98(4):1167-75
references.pmid: 16762022
references.citation: Mol Biol Cell. 2007 Dec;18(12):5060-8
references.pmid: 17928404
references.citation: J Neurochem. 2007 Nov;103(3):1228-36
references.pmid: 17727636
references.citation: Eur J Neurosci. 1997 Dec;9(12):2723-33
references.pmid: 9517477
references.citation: PLoS One. 2013;8(10):e76057
references.pmid: 24146816
references.citation: Arch Biochem Biophys. 1996 Apr 1;328(1):43-50
references.pmid: 8638936
references.citation: Int J Dev Neurosci. 2009 Oct;27(6):591-7
references.pmid: 19540327
references.citation: Neuroscience. 2011 Oct 13;193:330-7
references.pmid: 21763758
references.citation: Eur J Neurosci. 2009 Mar;29(6):1096-107
references.pmid: 19302146
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7445-50
references.pmid: 18495933
references.citation: J Neurosci. 2005 Jun 1;25(22):5446-54
references.pmid: 15930395