Axotomy-induced neurofilament phosphorylation is inhibited in situ by microinjection of PKA and PKC inhibitors into identified lamprey neurons.
Close axotomy of identified lamprey neurons induces phosphorylation of somatodendritic neurofilaments (NFs), followed by ectopic regeneration of neurofilamentous sprouts from the dendrites. We used in situ intracellular microinjection to study the mechanism of axotomy-induced NF phosphorylation. We found that inhibitors of protein kinase C (PKC) and protein kinase A (PKA) block somatodendritic NF phosphorylation for up to 15 days when injected at the time of axotomy. Injection of PKA catalytic subunit, diacylglycerol, or okadaic acid induces somatodendritic NF phosphorylation in intact neurons with the same time course as close axotomy. These results suggest that transient activation of PKC, PKA, and/or serine phosphatase inhibition by axotomy triggers persistent intracellular changes that may be related to polarity loss in these neurons.
Hall
G F
GF
Department of Neurology Neuroscience, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115.
Kosik
K S
KS
D000818:Animals; D001369:Axons / Q000502:physiology*; D003714:Denervation; D007395:Interneurons / Q000378:metabolism; D007798:Lampreys; D008845:Microinjections; D009046:Motor Neurons / Q000378:metabolism; D016900:Neurofilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D015290:Second Messenger Systems / Q000502:physiology
D016900:Neurofilament Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C