Phospho-Tau Protein Expression in the Cell Cycle of SH-SY5Y Neuroblastoma Cells: A Morphological Study

Article type: Research Article

Authors: Flores-Rodríguez, Paola^{a; b; e} | Harrington, Charles R.^c | Wischik, Claude M.^c | Ibarra-Bracamontes, Vanessa^{a; b} | Zarco, Natanael^a | Navarrete, Araceli^a | Martínez-Maldonado, Alejandra^{a; i} | Guadarrama-Ortíz, Parménides^d | Villanueva-Fierro, Ignacio^e | Ontiveros-Torres, Miguel Angel^f | Perry, George^g | Alonso, Alejandra D.^h | Floran-Garduño, Benjamin^a | Segovia, José^{a; *} | Luna-Muñoz, José^{b; *}

Affiliations: [a] Deparment of Physiology, Biophysics and Neuroscience, CINVESTAV, CDMX, México | [b] Brain Bank, Laboratorio Nacional de Servicios Experimentales, LaNSE-CINVESTAV, CDMX, México | [c] School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK | [d] Depto. de Neurocirugía, Centro Especializado en Neurocirugía y Neurociencias, México (CENNM), CDMX, México | [e] CIIDIR Durango, Instituto Politécnico Nacional, Becario COFAA, Durango, México | [f] School of Engineering and Science, Tecnologico de Monterrey, Toluca, México | [g] College of Sciences, University of Texas at San Antonio, TX, USA | [h] Biology Department and Center for Developmental Neuroscience, College of Staten Island, The City University of New York, Staten Island, NY, USA | [i] Anahuac University North Mexico, CDMX, México

Correspondence: [*] Correspondence to: José Luna-Muñoz, Brain Bank, Laboratorio Nacional de Servicios Experimentales, LaNSE-CINVESTAV, CDMX, México. E-mail: [email protected] and José Segovia, Department of Physiology, Biophysics and Neuroscience, CINVESTAV, CDMX, M_co. Tel.: +52 57473800; Ext: 1748; Fax: +52 57473800; Ext 5713; E-mail: [email protected].

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).

Keywords: Alzheimer’s disease, cell cycle, phospho-tau protein, SC35, SH-SY5Y, staurosporine

DOI: 10.3233/JAD-190155

Journal: Journal of Alzheimer's Disease, vol. 71, no. 2, pp. 631-645, 2019