The distributions of tau short and long isoforms fused with EGFP in cultured cells.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) are caused by mutations of the TAU gene. Many such mutations are located near the splicing site of exon 10 and affect the splicing ratio of 3-repeat/4-repeat tau isoforms (referred to as 3R-tau and 4R-tau) which contain 3 and 4 microtubule-binding domains, respectively. Little is known, however, concerning cellular localization of 3R-tau and 4R-tau. We examined the subcellular localization of tau isoforms in IMR-32 cells under differentiated conditions using the fusion proteins of tau isoforms probed with fluorescent protein (EGFP). 3R-tau was observed in spotty and rarely linear distributions while 4R-tau was observed in linear and sometimes spotty distributions. Together with findings of phase-contrast microscopy of cultured cells, these results indicated that 3R- and 4R-tau were predominantly localized at growth tips/branching points and along neurite processes, respectively. Due to their different localizations, balanced expression of 3R- and 4R-tau may coordinate plastic morphogenesis and stabilization of neurite processes.