FAST AXONAL-TRANSPORT OF KINESIN IN THE RAT VISUAL-SYSTEM - FUNCTIONALITY OF KINESIN HEAVY-CHAIN ISOFORMS

The mechanochemical ATPase kinesin is thought to move membrane-bounded organelles along microtubules in fast axonal transport. However, fast transport includes several classes of organelles moving at rates that differ by an order of magnitude. Further, the fact that cytoplasmic f orms of kinesin exist suggests that kinesins might move cytoplasmic st ructures such as the cytoskeleton. To define cellular roles for kinesi n, the axonal transport of kinesin was characterized. Retinal proteins were pulse-labeled, and movement of radiolabeled kinesin through opti c nerve and tract into the terminals was monitored by immunoprecipitat ion. Heavy and light chains of kinesin appeared in nerve and tract at times consistent with fast transport. Little or no kinesin moved with slow axonal transport indicating that effectively all axonal kinesin i s associated with membranous organelles. Both kinesin heavy chain mole cular weight variants of 130,000 and 124,000 M, (KHC-A and KHC-B) move d in fast anterograde transport, but KHC-A moved at 5-6 times the rate of KHC-B. KHC-A cotransported with the synaptic vesicle marker synapt ophysin, while a portion of KHC-8 cotransportee with the mitochondrial marker hexokinase. These results suggest that KHC-A is enriched on sm all tubulovesicular structures like synaptic vesicles and that at leas t one form of KHC-8 is predominantly on mitochondria. Biochemical spec ialization may target kinesins to appropriate organelles and facilitat e differential regulation of transport.