Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice.
Regulation of neurite outgrowth and structural plasticity may involve the expression of intrinsic determinants controlling growth competence. We have tested this concept by targeting constitutive expression of the growth-associated protein GAP-43 to the neurons of adult transgenic mice. Such mice showed striking spontaneous nerve sprouting at the neuromuscular junction and in the terminal field of hippocampal mossy fibers. In control mice, these nerve fibers did not express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting and terminal arborization during reinnervation were greatly potentiated in GAP-43-overexpressing mice. A mutant GAP-43 that cannot be phosphorylated by PKC had reduced sprout-promoting activity. The results establish GAP-43 as an intrinsic presynaptic determinant for neurite outgrowth and plasticity.
Aigner
L
L
Friedrich Miescher Institute, Basel, Switzerland.
Arber
S
S
Kapfhammer
J P
JP
Laux
T
T
Schneider
C
C
Botteri
F
F
Brenner
H R
HR
Caroni
P
P
D000818:Animals; D002645:Chickens / Q000235:genetics; D019922:GAP-43 Protein; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development*; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D009473:Neuronal Plasticity / Q000235:genetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012640:Seizures / Q000235:genetics
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D011493:Protein Kinase C