INHIBITION OF KINESIN SYNTHESIS IN-VIVO INHIBITS THE RAPID-TRANSPORT OF REPRESENTATIVE PROTEINS FOR 3 TRANSPORT VESICLE CLASSES INTO THE AXON

We have previously demonstrated that the in vivo vitreal injection of an antisense oligonucleotide directed to the kinesin heavy chain inhib its retinal kinesin synthesis by 82% and concomitantly inhibits rapid transport of total protein into the optic nerve by 70%. These results establish a major role for kinesin in rapid axonal transport in vivo. Recently, the cloning of a family of kinesin-like molecules from the m ammalian brain has been reported, and some of these proteins are also expressed in neurons. To assign a specific function to the kinesin hea vy chain we inhibited the kinesin synthesis with an antisense kinesin oligonucleotide and assessed the axonal transport into the optic nerve of representative proteins from each of three vesicle classes that co ntain rapidly transported proteins. Marker proteins used were substanc e P for peptide-containing synaptic vesicles, the amyloid precursor pr otein for plasma membrane precursor vesicles, and several integral syn aptic vesicle proteins. Our results indicate that the major anterograd e motor protein for all three vesicle classes utilizes kinesin heavy c hain, although we discuss alternative explanations.