Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The analysis of gene changes associated with exposure to cannabinoids is critical due to the multiple possible signaling pathways potentially affected by cannabinoid receptor activation. A comparison of altered gene profiles under two different conditions, one in vivo (chronic exposure to delta-9-THC) and the other in vitro (neuroprotection mediated by WIN55212-2), was made to determine whether it was possible to identify common genes that were affected. Up and down-regulated sets of genes are described. Genes affected in one or the other circumstance include alterations in a 14-3-3 regulator protein of PKC, CREB, BDNF and GABA receptor subunit proteins, as well as several genes associated with known cannabinoid receptor-coupled signaling pathways. Unexpectedly, several genes that were altered in both circumstances were associated with synaptic and membrane structure, motility and neuron growth. These included, neuronal cell adhesion molecule (NCAM), hyloronidan motility receptor, and myelin proteolipid protein. While the basis for involvement of these particular genes in cannabinoid receptor activated functional processes within the cell is still not well understood, awareness that significant numbers of genes and presumably proteins are changed following either acute or long-term exposure may provide new insight into their effects.
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PMID:Assessment of cannabinoid induced gene changes: tolerance and neuroprotection. 1250 5

Using a yeast two-hybrid screen, the neuronal membrane glycoprotein M6a, a member of the proteolipid protein family, was identified to be associated with the mu-opioid receptor (MOPr). Bioluminescence resonance energy transfer and co-immunoprecipitation experiments confirmed that M6a interacts agonist-independently with MOPr in human embryonic kidney 293 cells co-expressing MOPr and M6a. Co-expression of MOPr with M6a, but not with M6b or DM20, exists in many brain regions, further supporting a specific interaction between MOPr and M6a. After opioid treatment M6a co-internalizes and then co-recycles with MOPr to cell surface in transfected human embryonic kidney 293 cells. Moreover, the interaction of M6a and MOPr augments constitutive and agonist-dependent internalization as well as the recycling rate of mu-opioid receptors. On the other hand, overexpression of a M6a-negative mutant prevents mu-opioid receptor endocytosis, demonstrating an essential role of M6a in receptor internalization. In addition, we demonstrated the interaction of M6a with a number of other G protein-coupled receptors (GPCRs) such as the delta-opioid receptor, cannabinoid receptor CB1, and somatostatin receptor sst2A, suggesting that M6a might play a general role in the regulation of certain GPCRs. Taken together, these data provide evidence that M6a may act as a scaffolding molecule in the regulation of GPCR endocytosis and intracellular trafficking.
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PMID:Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling. 1754 56