MICROTUBULE-ASSOCIATED PROTEINS REGULATE MICROTUBULE FUNCTION AS THE TRACK FOR INTRACELLULAR MEMBRANE ORGANELLE TRANSPORTS

Axonal microtubules have two essential roles: providing the track for organelle transport and forming the cytoskeletal framework to maintain axonal morphology. Microtubule-associated proteins (MAPs) are essenti al for the formation of cytoskeletal architecture. However, they may h ave additional roles on the regulation of organelle transport by their interaction with motor proteins on the microtubules. We first examine d the effects of axonal MAPs on the organelle movement along microtubu les in a heterologous system using COS fibroblasts, which express no a xonal MAPs, such as tan or MAP2C. Transfection of tau or MAP2C gene su ppressed organelle movement almost completely in this cell type, hence interaction of axonal MAPs with microtubules interferes with organell e transports. It is known that the phosphorylation of MAPs reduces the ir interaction with microtubules. In this sense, phosphorylation of MA Ps can be a good candidate for the molecular switch to regulate the or ganelle transport. As a second set of experiments, we investigated the effects of modulating cAMP dependent protein kinase pathway on organe lle transports in primary sensory neurons, where high-molecular-weight tau protein is the major MAP. We found that the application of dibuty ryl cAMP enhanced transports of large organelles in the axon. Furtherm ore, this drug treatment phosphorylated endogenous tau protein and thu s reduced the affinity of tan to microtubules. These results indicate that axonal MAPs can work as a phosphorylation-dependent regulator of organelle transport. Local activation of protein kinase pathways in th e axon might play an important role on the segregation of microtubules serving for either organelle transport or cytoskeletal architecture.