HUMAN TAU-ISOFORMS CONFER DISTINCT MORPHOLOGICAL AND FUNCTIONAL-PROPERTIES TO STABLY TRANSFECTED FIBROBLASTS

Tau protein is a neuronal microtubule-associated protein that promotes the assembly and stability of microtubules. To evaluate the biologica l significance of tau isoform diversity, NIH-3T3 cells were stably tra nsfected with cDNAs encoding each of the six isoforms present in human brain. Cells expressing different isoforms developed distinct morphol ogies. Cell lines expressing 3-repeat tau isoforms developed large fla t cell bodies while cells expressing 4-repeat isoforms had small, roun d 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 d iffuse amorphous staining pattern that was concentrated around the cel l nucleus. Microtubule bundling was not enhanced in any of the transfe cted cells as compared to untransfected controls. The transfected cell s 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 depolyme rizing agent.