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Cannabinoid Receptor Interacting Protein 1a (CRIP1a) regulates CB1 signaling and transcriptional activity
Author(s) -
Blume Lawrence Christopher,
Bass Caroline E.,
Dalton George D.,
Selley Dana E.,
Howlett Allyn C.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.837.5
Subject(s) - cannabinoid receptor , neuroprotection , cannabinoid , signal transduction , biology , endocannabinoid system , g protein coupled receptor , microbiology and biotechnology , transcription factor , neuroscience , receptor , agonist , gene , genetics
The CB1 cannabinoid receptor is the most abundantly expressed GPCR in the CNS and modulates many diverse neuronal functions related to synaptic plasticity and neuroprotection. The cellular actions of CB1 ligands on neuroprotection are poorly understood. A recent demonstration that the cannabinoid receptor interacting protein (CRIP1a) had the ability to switch CB1 neuroprotection from an agonist‐ to antagonist‐driven mechanism is intriguing (Stauffer et al., 2011 Neuroscience Letters). To better understand the role of CRIP1a in cytoprotection, we developed neuronal cell models to over‐express or knock‐down CRIP1a in order to identify changes in CB1‐mediated signal transduction and gene transcription. Data from On‐cell‐Western experiments indicate that over‐expression of CRIP1a significantly reduces the levels of phosphoERK, a downstream kinase and transcript factor activated by CB1. Additional studies focusing on phospholipase C and NFkappaB pathways demonstrated that modulation of CRIP1a produces alterations in the mRNA levels of c‐Fos, CCAAT/Enhancer binding protein (Cebpb), NF‐kappaB pathway and genes involved in cell survival and neuroprotection. These experiments suggest that CRIP1a may modulate CB1 signaling and transcription of genes that are important in stress and cell survival pathways. Supported by NIH grants T32‐DA007246, R01‐DA003690, R21‐ DA025321, K01‐DA024763.