Premium
Plasma membrane and lysosomal localization of CB1 cannabinoid receptor are dependent on lipid rafts and regulated by anandamide in human breast cancer cells
Author(s) -
Sarnataro Daniela,
Grimaldi Claudia,
Pisanti Simona,
Gazzerro Patrizia,
Laezza Chiara,
Zurzolo Chiara,
Bifulco Maurizio
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.016
Subject(s) - lipid raft , cannabinoid receptor , anandamide , chemistry , receptor , microbiology and biotechnology , endocannabinoid system , cannabinoid , agonist , raft , endocrinology , biochemistry , biology , organic chemistry , copolymer , polymer
In 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.