TAU-REGULATION OF MICROTUBULE-MICROTUBULE SPACING AND BUNDLING

tau proteins are microtubule-associated proteins that promote microtub ule polymerization in vitro and in vivo. They are a family of neuronal proteins with apparent molecular weights in the range 50,000-68,000 d etermined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Recently, a new member of this family has been described and its cDN A has been cloned. It has an apparent molecular weight of 116,000 and has been called high-molecular-weight tau (HMW tau). All the tau prote ins are encoded by a single gene, which undergoes complex alternative splicing. In the present study, we have cloned into the baculovirus a cDNA fully encoding HMW tau as well as a truncated cDNA encoding a pro tein beginning 13 amino acids in front of the tau microtubule-binding domain. HMW tau-recombinant-virus-infected Sf9 cells overexpressed HMW tau, which induced the polymerization of microtubules and the formati on of long cellular processes similar to those induced by low-molecula r-weight tau (LMW tau) overexpression. Process cross sections revealed a larger spacing (approximate to 35 nm) between microtubules when ind uced by HMW tau than when induced by LMW tau (approximate to 20 nm). T he truncated construct also induces processes, where microtubules were packed far more closely together (approximate to 10 nm). Although bra nching did not occur in processes induced by intact tau s, 10% of the processes induced by the truncated tau protein branched.