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RESEARCH PRODUCT
The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons.
Christian NjooNitin AgarwalRohini KunerBeat Lutzsubject
MaleReceptor complexCannabinoid receptorDendritic spineQH301-705.5medicine.medical_treatmentDendritic SpinesNeurogenesisRecombinant Fusion ProteinsGrowth ConesWiskott-Aldrich Syndrome Protein NeuronalNerve Tissue ProteinsBiologyCannabinoidergicGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesActin remodeling of neurons0302 clinical medicineReceptor Cannabinoid CB1Parietal LobeChlorocebus aethiopsmedicineAnimalsBiology (General)Cells Cultured030304 developmental biologyMice KnockoutNeurons0303 health sciencesNeuronal PlasticityGeneral Immunology and MicrobiologyCannabinoidsGeneral NeuroscienceNeurogenesisActin cytoskeletonEmbryo MammalianCell biologyFrontal LobeMice Inbred C57BLActin CytoskeletonLuminescent Proteinsnervous systemCOS Cellslipids (amino acids peptides and proteins)CannabinoidGeneral Agricultural and Biological Sciences030217 neurology & neurosurgeryResearch Articledescription
The molecular composition of the cannabinoid type 1 (CB1) receptor complex beyond the classical G-protein signaling components is not known. Using proteomics on mouse cortex in vivo, we pulled down proteins interacting with CB1 in neurons and show that the CB1 receptor assembles with multiple members of the WAVE1 complex and the RhoGTPase Rac1 and modulates their activity. Activation levels of CB1 receptor directly impacted on actin polymerization and stability via WAVE1 in growth cones of developing neurons, leading to their collapse, as well as in synaptic spines of mature neurons, leading to their retraction. In adult mice, CB1 receptor agonists attenuated activity-dependent remodeling of dendritic spines in spinal cord neurons in vivo and suppressed inflammatory pain by regulating the WAVE1 complex. This study reports novel signaling mechanisms for cannabinoidergic modulation of the nervous system and demonstrates a previously unreported role for the WAVE1 complex in therapeutic applications of cannabinoids.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-12 | PLoS Biology |