Absence of GAP-43 can protect neurons from death.
The main function of GAP-43 is thought to be regulating growth cone motility and axon guidance signals. GAP-43 is highly expressed during development and in regenerating nerves and in particular regions of the adult brain. We here present the first evidence that GAP-43 can modulate guidance signals emanating from Semaphorin III (SemaIII) in cultured NGF-dependent sensory neurons. We further show that absence of GAP-43 dramatically increases resistance of specific sensory neurons to apoptotic stimuli in vitro. NGF-dependent sensory neurons from GAP-43 (+/-) and null mutant mice are strongly protected against SemaIII-induced death. Furthermore, NGF- and BDNF-dependent neurons, but not NT-3-dependent neurons, from GAP-43 null mutant mice are much more resistant to apoptosis induced by trophic factor deprivation. We also show that early postnatal Purkinje cells from GAP-43 (+/-) mice are more resistant to cell death in organotypic cultures. We conclude that GAP-43 can influence neuronal survival and modulate repulsive axon guidance signals.
Gagliardini
V
V
Brain Research Institute, Department of Neuromorphology, University of Zurich and Swiss Federal Institute of Technology Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
Dusart
I
I
Fankhauser
C
C
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D019922:GAP-43 Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D040121:Semaphorin-3A
D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D006023:Glycoproteins; D040121:Semaphorin-3A; D020932:Nerve Growth Factor