title: Alterations in the nuclear architecture produced by the overexpression of tau protein in neuroblastoma cells.
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.
authors: Center of Research and Advanced Studies, Department of Cell Biology, National Polytechnic Institute, Av. Instituto Politecnico Nacional 2508, Mexico City, Mexico.
authors: Hugo C
authors: HC
authors: Monroy-Ramírez
authors: Gustavo
authors: G
authors: Basurto-Islas
authors: Raul
authors: R
authors: Mena
authors: Bulmaro
authors: B
authors: Cisneros
authors: Lester I
authors: LI
authors: Binder
authors: Jesús
authors: J
authors: Avila
authors: Francisco
authors: F
authors: Garcia-Sierra
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014404:Tubulin; D016875:tau Proteins