Phosphorylation-dependent immunoreactivity of neurofilaments increases during axonal maturation and beta,beta'-iminodipropionitrile intoxication.
The immunoreactivity of the high-molecular-weight neurofilament (NF) subunit toward antibodies that react with phosphorylation-related epitopes was determined at different anatomic sites in the PNS of rats during normal maturation and after intoxication with beta,beta'-iminodipropionitrile (IDPN). A maturational increase in the relative binding of phosphorylation-dependent antibodies compared to phosphorylation-inhibited antibodies occurred from age 3 to 12 weeks. An increase in phosphorylation-related immunoreactivity with increasing distance from the cell bodies was present in ventral and dorsal roots at all ages. The degree of phosphorylation-related immunoreactivity was greater for centrally directed axons in the dorsal roots of the L5 ganglion than for peripherally directed axons. IDPN, a toxin that impairs NF transport, caused a marked increase in reactivity toward the phosphorylation-dependent antibody. NFs from IDPN-treated rats also bound less of an antibody that is normally phosphorylation independent and this inhibition of binding was sensitive to phosphatase digestion. In each instance, greater degrees of phosphorylation-dependent immunoreactivity correlate with conditions known to exhibit slower net rates of axonal transport of NF proteins.
Watson
D F
DF
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Griffin
J W
JW
Fittro
K P
KP
Hoffman
P N
PN
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D007381:Intermediate Filament Proteins / Q000276:immunology / Q000378:metabolism*; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D000939:Epitopes; D007381:Intermediate Filament Proteins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile