Activation of protein kinase C inhibits retrograde transport of neurotrophins in mice.
Retrograde axonal transport of neurotrophins from nerve terminal to cell body requires a number of key processes, including internalization of the receptor-neurotrophin complex into vesicles and formation of multivesicular bodies and their transport along the axon. Previous studies have shown that each of these processes can be regulated by kinases. In this study, we looked at the role of protein kinase C (PKC) in retrograde transport by injecting labeled neurotrophins together with relevant pharmacological agents into the eye and measuring the accumulation of radioactivity in the trigeminal and superior cervical ganglia. Inhibitors of PKC, Ro-31-8220 and rottlerin, did not affect the retrograde transport of nerve growth factor (NGF); however, phorbol ester activation of classical and novel PKCs blocked retrograde transport. The effect of phorbol esters was partially reversed by rottlerin and Ro-31-8220. Activation of PKC has been shown to be involved in the disorganization of actin filaments. In this study, we show that Ro-31-8220 reverses growth cone collapse by phorbol 12-myristate 13-acetate and suggest that one of the effects of activating PKC on retrograde transport is to disrupt the actin filaments.
Ozsarac
Nesrin
N
Developmental Neurobiology Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. nesrin.ozsarac@anu.edu.au
Weible
Michael
M
Reynolds
Anna J
AJ
Hendry
Ian A
IA
D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye / Q000294:innervation / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000378:metabolism
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007211:Indoles; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220