Affiliations: [a] Center of Research and Advanced Studies of the IPN, Department of Cell Biology, Mexico City, Mexico | [b] Departamento de Ciencias Naturales, DCNI, Universidad Autonoma Metropolitana, Unidad Cuajimalpa, Mexico D.F., Mexico | [c] Center of Research and Advanced Studies of the IPN, Department of Physiology Biophysics and Neuroscience, Mexico City, Mexico | [d] Center of Research and Advanced Studies of the IPN, Department of Genetics and Molecular Biology, Mexico City, Mexico | [e] Cognitive Neurology and Alzheimer's Disease Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA | [f] Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain
Correspondence:
[*]
Correspondence to: Francisco García-Sierra, Ph.D., Center of Research and Advanced Studies of the National Polytechnic Institute, Department of Cell Biology, Av. Instituto Politecnico Nacional 2508, CP 07360, Mexico city, Mexico. Tel.: +52 555 747 33 54; Fax: +52 555 747 33 93; E-mails: [email protected]; [email protected].
Abstract: Abnormal intracellular aggregation of tau protein is a pathological condition leading to neuronal death in Alzheimer's disease. Fibrillar and nonfibrillar aggregates of tau protein alter the normal functioning of neurons by disturbing important cellular processes and distinct membranous organelles. However, tau-caused alterations in the nuclear compartment are not totally established so far. In our study we evaluated whether tau protein and its Asp421-truncated variant produce alterations in the normal architecture of the nucleus when expressed in cultured neuroblastoma cells. After 48 hours of transfection, significant deformity of the nuclear compartment with extensive lobulations along the nuclear envelope was observed in SH-SY5Y cells expressing either full-length tau or Asp421-truncated tau. This aberrant formation did not involve either nuclear fragmentation or cell death. The lobulated nuclei were devoid of tau protein, which mostly remained in the cytoplasm in a nonfibrillar state. Degradation of nuclear Lamins was not observed in tau-expressing SH-SY5Y cells, and a cell-cycle analysis did not show aberrant chromosome accumulation. Thus multiple division defects leading to multinucleation were discarded. The lobulated nuclei in tau-expressing SH-SY5Y cells seem to more resemble the multilobular phenotype of the nuclear envelope seen in Lamin-mutated cells from those pathological conditions leading to premature aging. Nevertheless, in our tau-expressing cells, the abnormal formation of cortical and perinuclear rings of tubulin generated by tau binding may be a more feasible mechanism of a nuclear-cytoskeleton generating force that causes the nuclear deformation.
Keywords: Alzheimer's disease, confocal microscopy, Lamins, microtubules, nuclear architecture, tau pathology, truncated tau
