SENSE AND ANTISENSE TRANSFECTION ANALYSIS OF TAU-FUNCTION - TAU-INFLUENCES NET MICROTUBULE ASSEMBLY, NEURITE OUTGROWTH AND NEURITIC STABILITY

Microtubules are fundamental elements participating in many aspects of cell behavior and maintenance, yet the factors regulating microtubule behavior in vivo remain poorly understood. Employing the nerve growth factor (NGF)-responsive cell line, PC12, we have used sense and antis ense DNA transfection strategies to examine the role of the microtubul e-associated protein (MAP) tau in several aspects of neuronal cell beh avior. Stable transfectants overexpressing tao accumulate more microtu bule mass and extend neurites more rapidly than control cells, while t ransfectants under-expressing tau exhibit reduced microtubule levels a nd slower neurite outgrowth. Further, tau over-expressing cells are ma rkedly more resistant to nocodazole-induced neuritic degeneration when compared to wild-type or tau under-expressing cells. These observatio ns provide direct support for the model that tau is capable of influen cing: (i) net microtubule assembly, (ii) the rate of neurite elongatio n and (iii) neuritic stability. These capabilities suggest that tau pl ays crucial roles in the development and maintenance of neuronal cells .