TAU BINDS TO THE DISTAL AXON EARLY IN DEVELOPMENT OF POLARITY IN A MICROTUBULE-DEPENDENT AND MICROFILAMENT-DEPENDENT MANNER

Microtubule-associated protein tau is localized to the axon in situ an d has been implicated in the development of neuronal polarity, Here we report that tau is extracted differentially in cultured hippocampal n eurons yielding an axon-specific localization under conditions that ke ep the integrity of the plasma membrane. The amount of bound tau incre ases toward the distal axon and is highest at the transition from the axonal shaft to the growth cone. This distribution is significantly di fferent from the distribution of axonal microtubules that are most con centrated at the proximal axon. Distal binding of tau to one process a ppears early in development of polarity in culture and correlates with the onset of axon formation (day 2 in culture). Binding to the distal axon requires intact microtubules and microfilaments. Distal tau bind ing does not stabilize microtubules selectively against drug-induced d isassembly, because colchicine-induced microtubule depolymerization is highest distally. We conclude that binding of tau to the distal axon follows a complex mechanism, is an early event in the development of p olarity, and reproduces the axon-specific localization of tau in situ.