Plasma membrane and lysosomal localization of CB1 cannabinoid receptor are dependent on lipid rafts and regulated by anandamide in human breast cancer cells

6533b874fe1ef96bd12d6438

RESEARCH PRODUCT

Plasma membrane and lysosomal localization of CB1 cannabinoid receptor are dependent on lipid rafts and regulated by anandamide in human breast cancer cells

Chiara Zurzolo Chiara Zurzolo Simona Pisanti Chiara Laezza Daniela Sarnataro Daniela Sarnataro Maurizio Bifulco Maurizio Bifulco Patrizia Gazzerro Claudia Grimaldi

subject

CB1 receptor Cannabinoid receptor MESH: Membrane Microdomains MESH: Receptor Cannabinoid CB1 Biochemistry chemistry.chemical_compound Rafts MESH: Cholesterol 0302 clinical medicine Receptor Cannabinoid CB1 Structural Biology Receptor Lipid raft 0303 health sciences Chemistry beta-Cyclodextrins Anandamide Endocannabinoid system 3. Good health Cell biology Cholesterol lipids (amino acids peptides and proteins)Agonist MESH: beta-Cyclodextrins MESH: Cell Line Tumor Polyunsaturated Alkamides medicine.drug_class Biophysics Breast Neoplasms Arachidonic Acids 03 medical and health sciences Membrane Microdomains Cell Line Tumor Genetics medicine MESH: Arachidonic Acids Humans Molecular Biology 030304 developmental biology G protein-coupled receptor MESH: Humans MESH: Polyunsaturated Alkamides Cell Membrane [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Anandamide Cell Biology Caveolin 1 Lysosomes Intracellular trafficking MESH: Breast Neoplasms 030217 neurology & neurosurgery MESH: Cell Membrane MESH: Lysosomes Endocannabinoids

description

AbstractIn this report we show, by confocal analysis of indirect immunofluorescence, that the type-1 cannabinoid receptor (CB1R), which belongs to the family of G-protein-coupled receptors, is expressed on the plasma membrane in human breast cancer MDA-MB-231 cells. However, a substantial proportion of the receptor is present in lysosomes. We found that CB1R is associated with cholesterol- and sphyngolipid-enriched membrane domains (rafts). Cholesterol depletion by methyl-β-cyclodextrin (MCD) treatment strongly reduces the flotation of the protein on the raft-fractions (DRM) of sucrose density gradients suggesting that CB1 raft-association is cholesterol dependent. Interestingly binding of the agonist, anandamide (AEA) also impairs DRM-association of the receptor suggesting that the membrane distribution of the receptor is dependent on rafts and is possibly regulated by the agonist binding. Indeed MCD completely blocked the clustering of CB1R at the plasma membrane. On the contrary the lysosomal localization of CB1R was impaired by this treatment only after AEA binding.

year	journal	country	edition	language
2005-11-21

10.1016/j.febslet.2005.10.016 http://hdl.handle.net/11588/113046