Human tau isoforms confer distinct morphological and functional properties to stably transfected fibroblasts

Abstract Tau protein is a neuronal microtubule-associated protein that promotes the assembly and stability of microtubules. To evaluate the biological significance of tau isoform diversity, NIH-3T3 cells were stably transfected with cDNAs encoding each of the six isoforms present in human brain. Cells expressing different isoforms developed distinct morphologies. Cell lines expressing 3-repeat tau isoforms developed large flat cell bodies while cells expressing 4-repeat isoforms had small, round cell bodies. All transfected cell lines, except those expressing the shortest tau isoform, displayed very long thin neurite-like processes. Tau colocalized with microtubules in both the cell body and the long processes in all of the tau-transfected cells. Tau also displayed a diffuse amorphous staining pattern that was concentrated around the cell nucleus. Microtubule bundling was not enhanced in any of the transfected cells as compared to untransfected controls. The transfected cells showed increased resistance to colchicine treatment. Thus, different tau isoforms can confer unique cellular morphologies to 3T3 cells and can alter the susceptibility of these cells to a microtubule depolymerizing agent.