Cyclic guanosine monophosphate signalling pathway plays a role in neural cell adhesion molecule-mediated neurite outgrowth and survival.
The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, regeneration, and synaptic plasticity associated with learning and memory consolidation. Homophilic binding of NCAM leads to neurite extension and neuroprotection in various types of primary neurons through activation of a complex network of signalling cascades, including fibroblast growth factor receptor, Src-family kinases, the mitogen-activated protein kinase pathway, protein kinase C, phosphatidylinositol-3 kinase, and an increase in intracellular Ca(2+). Here we present data indicating an involvement of cyclic GMP in NCAM-mediated neurite outgrowth in both hippocampal and dopaminergic neurons and in NCAM-mediated neuroprotection of dopaminergic neurons. In addition, evidence is presented suggesting that NCAM mediates activation of cGMP via synthesis of nitric oxide (NO) by NO synthase (NOS) and activation of soluble guanylyl cyclase by NO, leading to an increased synthesis of cGMP and activation by cGMP of protein kinase G.
Ditlevsen
Dorte Kornerup
DK
Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute 6.2, Copenhagen, Denmark.
Køhler
Lene Boding
LB
Berezin
Vladimir
V
Bock
Elisabeth
E
D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D006624:Hippocampus / Q000166:cytology; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
D004791:Enzyme Inhibitors; D019006:Neural Cell Adhesion Molecules; C016276:8-bromocyclic GMP; D006152:Cyclic GMP