R. Satoharada et al., MICROTUBULE-ASSOCIATED PROTEINS REGULATE MICROTUBULE FUNCTION AS THE TRACK FOR INTRACELLULAR MEMBRANE ORGANELLE TRANSPORTS, Cell structure and function, 21(5), 1996, pp. 283-295
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.