THE ACTIVATION OF PROTEIN-KINASE A PATHWAY SELECTIVELY INHIBITS ANTEROGRADE AXONAL-TRANSPORT OF VESICLES BUT NOT MITOCHONDRIA TRANSPORT OR RETROGRADE TRANSPORT IN-VIVO
Y. Okada et al., THE ACTIVATION OF PROTEIN-KINASE A PATHWAY SELECTIVELY INHIBITS ANTEROGRADE AXONAL-TRANSPORT OF VESICLES BUT NOT MITOCHONDRIA TRANSPORT OR RETROGRADE TRANSPORT IN-VIVO, The Journal of neuroscience, 15(4), 1995, pp. 3053-3064
To shed light on how axonal transport is regulated, we examined the po
ssible roles of protein kinase A (PKA) in vivo suggested by our previo
us work (Sato-Yoshitake et al., 1992), Pharmacological probes or the p
urified catalytic subunit of PKA were applied to the permeabilized-rea
ctivated model of crayfish walking leg giant axon, and the effect was
monitored by the quantitative video-enhanced light microscopy and the
quantitative electron microscopy, Dibutyryl cyclic AMP caused concentr
ation-dependent transient reduction in the number of anterogradely tra
nsported small vesicles, while the retrogradely transported organelles
and anterogradely transported mitochondria showed no decrease, This t
ransient selective inhibition of anterograde vesicle transport was rev
ersed by the application of a specific inhibitor of PKA (KT5720) in a
concentration-dependent manner, and was reproduced by the application
of the purified catalytic subunit of PKA and augmented by the applicat
ion of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S). Correspondin
g biochemical study showed that several axoplasmic proteins including
kinesin were specifically phosphorylated by the activation of the PKA
pathway, These findings suggest the possible roles of PKA in the regul
ation of the direction of the axonal transport in vivo. The finding th
at only vesicle transport but not mitochondria transport was inhibited
also suggests that the transport of vesicles and that of mitochondria
are differently regulated and might be supported by different motors.