Conventional kinesin-I motors participate in the anterograde axonal transport of neurotrophins in the visual system.
Retinal ganglion cells (RGCs) anterogradely transport neurotrophins to the midbrain tectum/superior colliculus with significant downstream effects. The molecular mechanism of this type of axonal transport of neurotrophins is not well characterized. We identified kinesin-I proteins as a motor participating in the anterograde axonal movement of vesicular structures containing radiolabeled neurotrophins along the optic nerve. RT-PCR analysis of purified murine RGCs showed that adult RGCs express all known members of the kinesin-I family. After intraocular injection of (125)I-brain-derived neurotrophic factor (BDNF) into the adult mouse or (125)I-neurotrophin-3 (NT-3) into the embryonic chicken eye, radioactivity was efficiently immunoprecipitated from the optic nerve lysates by anti-kinesin heavy chain and anti-kinesin light chain monoclonal antibodies (H2 and L1). Immunoreactivity for the BDNF receptor trkB is also present in the immunoprecipitates obtained by the anti-kinesin-I antibodies. The delivery of the H2 antibody in vivo into the mouse RGCs substantially reduced anterograde axonal transport of (125)I-BDNF. Anterograde transport of BDNF was not diminished in kinesin light chain 1 (KLC1) knockout mice. However, this may be due to redundancy in functions between two different isoforms of KLC present in the RGCs, as it was described previously for kinesin heavy chains (Kanai et al. [ 2000] J Neurosci 20:6374-6384). These data indicate that kinesin-I is a protein motor that participates in the anterograde axonal transport of neurotrophins in the chicken and mouse visual pathways.
Butowt
Rafal
R
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA. rafalbutowt@yahoo.com
von Bartheld
Christopher S
CS
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001370:Axonal Transport / Q000502:physiology*; D002642:Chick Embryo; D047468:Immunoprecipitation / Q000379:methods; D007456:Iodine Isotopes / Q000378:metabolism; D016547:Kinesins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency; D009414:Nerve Growth Factors / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012165:Retinal Ganglion Cells / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014795:Visual Pathways / Q000378:metabolism* / Q000648:ultrastructure
D007456:Iodine Isotopes; C000715695:Kns2 protein, mouse; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016547:Kinesins