TAU-ISOFORM EXPRESSION AND PHOSPHORYLATION STATE DURING DIFFERENTIATION OF CULTURED NEURONAL CELLS

The axonal microtubule-associated protein, tau, is thought to play an important role in axonal growth and in the establishment of neuronal polarity, In adult human brain there are six alternatively spliced tau isoforms, which have different microtubule binding affinities in vitro, The tubulin-tau interaction is further modified by phosphorylation of tan and, compared to adult brain tan, both foetal brain tau and paired helical filament (PHF) tau, characteristic of Alzheimer's disease, are hyperphosphorylated, In vivo both the expression of tau isoforms and their phosphorylation states are developmentally regulated, In order to establish the correlation between the expression of tau isoforms and their pattern of phosphorylation, we have characterised these two features in several in vitro models of neuronal differentiation, including the human neuroblastoma cell lines, SK-N-SH, SH-SY5Y and IMR32 cells, rat PC12 cells and primary rat cortical neurones, Sensitive RT-PCR analysis revealed a different complement of tau isoforms in the different cell lines and neuritogenesis was associated mainly with an increase in the overall tau protein level with no apparent phosphorylation changes, A switch in tan isoform expression occurred only at the terminal stages of neuronal development, when it may be important in reinforcing the previously established axonal cytoarchitecture.