Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three 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 inhibits 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 mammalian brain has been reported, and some of these proteins are also expressed in neurons. To assign to specific function to the kinesin heavy 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 contain rapidly transported proteins. Marker proteins used were substance P for peptide-containing synaptic vesicles, the amyloid protein for plasma membrane precursor vesicles, and several integral synaptic vesicle proteins. Our results indicate that the major anterograde motor protein for all three vesicle classes utilizes kinesin heavy chain, although we discuss alternative explanations.
Amaratunga
A
A
Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.
Leeman
S E
SE
Kosik
K S
KS
Fine
R E
RE
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002135:Calcium-Binding Proteins; D007163:Immunosorbent Techniques; D016547:Kinesins / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009900:Optic Nerve / Q000378:metabolism*; D011817:Rabbits; D013373:Substance P / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins
D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D016708:Synaptophysin; D050857:Synaptotagmins; D013373:Substance P; D016547:Kinesins