Absence of GAP-43 can protect neurons from death

Mol Cell Neurosci. 2000 Jul;16(1):27-33. doi: 10.1006/mcne.2000.0850.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • Apoptosis* / drug effects
  • Axons / metabolism
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Survival / genetics
  • Cells, Cultured
  • GAP-43 Protein / deficiency*
  • GAP-43 Protein / genetics
  • GAP-43 Protein / metabolism
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Glycoproteins / pharmacology
  • Growth Cones / drug effects
  • Mice
  • Mice, Knockout
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / pharmacology
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism*
  • Purkinje Cells / cytology
  • Purkinje Cells / metabolism
  • Semaphorin-3A

Substances

  • Antigens, Differentiation
  • Brain-Derived Neurotrophic Factor
  • GAP-43 Protein
  • Glycoproteins
  • Semaphorin-3A
  • Nerve Growth Factor