Uncorrected Author Proof Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-190155 IOS Press 1 Phospho-Tau Protein Expression in the Cell Cycle of SH-SY5Y Neuroblastoma Cells: A Morphological Study 1 2 3 Paola Flores-Rodr´ ıguez a,b , Charles R. Harrington c , Claude M. Wischik c , Vanessa Ibarra-Bracamontes a,b , Natanael Zarco a , Araceli Navarrete a , Alejandra Mart´ ınez-Maldonado a,i , Parm´ enides Guadarrama-Ort´ ız d , Ignacio Villanueva-Fierro e , Miguel Angel Ontiveros-Torres e , George Perry f , Alejandra D. Alonso g , Benjamin Floran-Gardu ˜ no a , Jos´ e Segovia a,∗ and Jos´ e Luna-Mu ˜ noz b,∗ 4 5 6 7 8 a Deparment of Physiology, Biophysics and Neuroscience, CINVESTAV, CDMX, M´ exico 9 b Brain Bank, Laboratorio Nacional de Servicios Experimentales, LaNSE-CINVESTAV, CDMX, M´ exico 10 c School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK 11 d Depto. de Neurocirug´ ıa, Centro Especializado en Neurocirug´ ıa y Neurociencias, M´ exico (CENNM), CDMX, M´ exico 12 13 e CIIDIR Durango, Instituto Polit´ ecnico Nacional, Becario COFAA, Durango, M´ exico 14 f School of Engineering and Science, Tecnologico de Monterrey, Toluca, M´ exico 15 g College of Sciences, University of Texas at San Antonio, TX, USA 16 h Biology Department and Center for Developmental Neuroscience, College of Staten Island, The City University of New York, Staten Island, NY, USA 17 18 i Anahuac University North Mexico, CDMX, M´ exico 19 Handling Editor: Jesus Avila 20 Accepted 11 July 2019 Abstract. It has been reported that the main function of tau protein is to stabilize microtubules and promote the movement of organelles through the axon in neurons. In Alzheimer’s disease, tau protein is the major constituent of the paired helical filament, and it undergoes post-translational modifications including hyperphosphorylation and truncation. Whether other functions of tau protein are involved in Alzheimer’s disease is less clear. We used SH-SY5Y human neuroblastoma cells as an in vitro model to further study the functions of tau protein. We detected phosphorylated tau protein as small dense dots in the cell nucleus, which strongly colocalize with intranuclear speckle structures that were also labelled with an antibody to SC35, a protein involved in nuclear RNA splicing. We have shown further that tau protein, phosphorylated at the sites recognized by pT231, TG-3, and AD2 antibodies, is closely associated with cell division. Different functions may be characteristic of phosphorylation at specific sites. Our findings suggest that the presence of tau protein is involved in separation of sister chromatids in anaphase, and that tau protein also participates in maintaining the integrity of the DNA (pT231, prophase) and chromosomes during cell division (TG-3). 21 22 23 24 25 26 27 28 29 30 31 Keywords: Alzheimer’s disease, cell cycle, phospho-tau protein, SC35, SH-SY5Y, staurosporine 32 ∗ Correspondence to: Jos´ e Luna-Mu ˜ noz, Brain Bank, Laborato- rio Nacional de Servicios Experimentales, LaNSE-CINVESTAV, CDMX, M´ exico. E-mail: jluna@cinvestav.mx and Jos´ e Segovia, Department of Physiology, Biophysics and Neuroscience, CIN- VESTAV, CDMX, México. Tel.: +52 57473800; Ext: 1748; Fax: +52 57473800; Ext 5713; E-mail: jsegovia@fisio.cinvestav.mx. ISSN 1387-2877/19/$35.00 © 2019 – IOS Press and the authors. All rights reserved