scholarly journals Design Logic of a Cannabinoid Receptor Signaling Network That Triggers Neurite Outgrowth

Science ◽  
2008 ◽  
Vol 320 (5878) ◽  
pp. 903-909 ◽  
Author(s):  
K. D. Bromberg ◽  
A. Ma'ayan ◽  
S. R. Neves ◽  
R. Iyengar
2006 ◽  
Vol 84 (7) ◽  
pp. 687-694 ◽  
Author(s):  
John Cijiang He ◽  
Susana R. Neves ◽  
J. Dedrick Jordan ◽  
Ravi Iyengar

Neurite outgrowth is a complex differentiation process stimulated by many neuronal growth factors and transmitters and by electrical activity. Among these stimuli are ligands for G-protein-coupled receptors (GPCR) that function as neurotransmitters. The pathways involved in GPCR-triggered neurite outgrowth are not fully understood. Many of these receptors couple to Gαo, one of the most abundant proteins in the neuronal growth cones. We have studied the Go signaling network involved in neurite outgrowth in Neuro2A cells. Gαo can induce neurite outgrowth. The CB1 cannabinoid receptor, a Go/i-coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1, which promotes the Gαo-stimulated proteasomal degradation of Rap1GAPII. CB1-receptor-mediated Rap1 activation leads to the activation of a signaling network that includes the small guanosine triphosphate (GTP)ases Ral and Rac, the protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the activation of signal transducer and activator of transcription 3 (Stat3), a key transcription factor that mediates the gene expression process of neurite outgrowth in Neuro2A cells. This review describes current findings from our laboratory and also discusses alternative pathways that Go/i might mediate to trigger neurite outgrowth. We also analyze the role neurotransmitters, which stimulate Go/i to activate a complex signaling network controlling neurite outgrowth, play in regeneration after neuronal injury.


2013 ◽  
Vol 52 (4) ◽  
pp. 633-650 ◽  
Author(s):  
Ismael Galve-Roperh ◽  
Valerio Chiurchiù ◽  
Javier Díaz-Alonso ◽  
Monica Bari ◽  
Manuel Guzmán ◽  
...  

2011 ◽  
Vol 11 (2) ◽  
pp. M111.014613 ◽  
Author(s):  
Jason D. Hoffert ◽  
Trairak Pisitkun ◽  
Fahad Saeed ◽  
Jae H. Song ◽  
Chung-Lin Chou ◽  
...  

2018 ◽  
Vol 42 (4) ◽  
pp. 718-726 ◽  
Author(s):  
Dal Khatri ◽  
Genevieve Laroche ◽  
Marion L. Grant ◽  
Victoria M. Jones ◽  
Ryan P. Vetreno ◽  
...  

2020 ◽  
Vol 22 (3) ◽  
pp. 207-222

The endocannabinoid system (ECS) is a highly versatile signaling system within the nervous system. Despite its widespread localization, its functions within the context of distinct neural processes are very well discernable and specific. This is remarkable, and the question remains as to how such specificity is achieved. One key player in the ECS is the cannabinoid type 1 receptor (CB1), a G protein–coupled receptor characterized by the complexity of its cell-specific expression, cellular and subcellular localization, and its adaptable regulation of intracellular signaling cascades. CB1 receptors are involved in different synaptic and cellular plasticity processes and in the brain’s bioenergetics in a context-specific manner. CB2 receptors are also important in several processes in neurons, glial cells, and immune cells of the brain. As polymorphisms in ECS components, as well as external impacts such as stress and metabolic challenges, can both lead to dysregulated ECS activity and subsequently to possible neuropsychiatric disorders, pharmacological intervention targeting the ECS is a promising therapeutic approach. Understanding the neurobiology of cannabinoid receptor signaling in depth will aid optimal design of therapeutic interventions, minimizing unwanted side effects.


2005 ◽  
Vol 280 (39) ◽  
pp. 33426-33434 ◽  
Author(s):  
John Cijiang He ◽  
Ivone Gomes ◽  
Tracy Nguyen ◽  
Gomathi Jayaram ◽  
Prahlad T. Ram ◽  
...  

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