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

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).

Human Dental Pulp Stem Cells Display a Potential for Modeling Alzheimer Disease-Related Tau Modifications

“…Remarkably, the TG3 antibody was the only one in the panel that labeled tau in mitotic chromosomes at all phases of the mitosis (Figure 4A) in agreement with the observation by others (28,38,72). We found rare cells at the anaphase-telophase phases showing low tau amounts in recently reformed nuclei ( Supplementary Figure 3C), which, along with the above shown presence of tau in mitotic chromosomes, suggests that tau appears in mitosis and disappears in the nuclei of interphase cells.…”

“…Tau has also been evidenced in oligodendrocytes (23), in astrocytes (24), and in some nonneural cells, such as skin fibroblasts (25). Tau function and pathogenesis are restricted to the cytoplasm; hence, the meaning of its presence in nuclei (26)(27)(28) remains generally understudied. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease.…”

PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer’s Disease

“…Tau is a stabilizing microtubule-associated protein. In the nucleus, this protein protects the DNA in situations of cellular stress; in the nucleolus, it favors the nucleolar function ( Sjoberg et al, 2006 ), the process of mitosis ( Flores-Rodriguez et al, 2019 ) and meiosis ( Inoue et al, 2014 ). Tau has been previously observed in non-neuronal organs such as the heart, skeletal muscle, lung, or skin and in different states of non-pathological phosphorylation ( Gu et al, 1996 ; Zhou et al, 2020 ).…”

Tau: More than a microtubule‐binding protein in neurons

“…Tau has consistently been detected in the nucleus (Brady et al, 1995; Bukar Maina et al, 2016; Cross et al, 2000; Flores‐Rodriguez et al, 2019; Frost et al, 2015; Greenwood & Johnson, 1995). It has long been suggested that tau can be phosphorylated in the cytoplasm and then translocated into the nucleus, where it cannot be phosphorylated (Greenwood & Johnson, 1995).…”