Evidence for the coidentification of GAP-43, a growth-associated protein, and F1, a plasticity-associated protein.
GAP-43 is a fast-axonally transported protein whose expression correlates with periods of axon growth both during development and during regeneration. Similarities in molecular weight (43-47 kDa), pI (4.3-4.5), and aberrant behavior in acrylamide gels suggested that GAP-43 might be related or identical to protein F1, a protein kinase C substrate that has been shown to undergo a change in phosphorylation state during long-term potentiation in the hippocampus. Here we show that GAP-43 and protein F1 comigrate by two-dimensional PAGE and that antiserum raised against GAP-43 specifically immunoprecipitates protein F1. More direct evidence that GAP-43 and protein F1 are identical proteins was obtained by performing S. aureus V8 protease digests of a mixture of purified 32P-labeled protein F1 and purified GAP-43. Under these conditions, 2 phosphorylated peptide fragments of protein F1 corresponded exactly to 2 Coomassie-stainable bands from purified GAP-43. We conclude on the basis of these data that GAP-43 and protein F1 are identical proteins. Using light-microscopic immunocytochemistry, we also show that GAP-43/protein F1 immunoreactivity is localized to neuropil areas of the hippocampus consistent with its roles as a protein kinase C substrate in vivo and in long-term potentiation. These findings suggest that nerve growth during development and regeneration, and synaptic plasticity in the adult mammalian brain, may be mediated by a common mechanism involving the phosphorylation of GAP-43/protein F1.
Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
G J
GJ
Snipes
S Y
SY
Chan
C B
CB
McGuire
B R
BR
Costello
J J
JJ
Norden
J A
JA
Freeman
A
A
Routtenberg
D000818:Animals; D001923:Brain Chemistry; D019922:GAP-43 Protein; D008565:Membrane Proteins / Q000032:analysis / Q000302:isolation & purification* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000302:isolation & purification* / Q000378:metabolism; D009473:Neuronal Plasticity; D010750:Phosphoproteins / Q000032:analysis / Q000302:isolation & purification* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D019922:GAP-43 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins