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Τετάρτη 26 Ιουλίου 2017

Palmitoylation is a prerequisite for dimerization-dependent raftophilicity of rhodopsin [Membrane Biology]

The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled receptor (GPCR) responsible for initiation of the phototransduction cascade in rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher oligomers, and tends to have a supramolecular organization that is likely important in the dim light response. Rh also exhibits high affinity for lipid rafts (raftophilicity) upon light-dependent binding with cognate G protein transducin (Gt), suggesting the presence of lipid raft-like domains in the retinal disk membrane and their importance in phototransduction. However, the relationship between Rh oligomerization and lipid rafts in the disk membrane remains to be explored. Given previous findings that Gt binds to dimeric Rh and Rh is post-translationally modified with two highly raftophilic palmitoyl moieties, we hypothesized that Rh becomes raftophilic upon dimerization. Here, we tested this hypothesis biochemically. First, we found that Rh*-Gt complexes in the detergent-resistant membrane (DRM) are partially resistant to cholesterol depletion by methyl-β-cyclodextrin (MCD), and the stoichiometry of Rh to Gt in this MCD-resistant complex is 2:1. We then found that IgG-crosslinking renders Rh highly raftophilic, supporting the premise that Rh becomes raftophilic upon dimerization. Depalmitoylation of Rh with the reduction of thioester linkages by dithiothreitol blocked the translocation of IgG-crosslinked Rh to the DRM, highlighting the importance of the two palmitoyl moieties in the dimerization-dependent raftophilicity of Rh. These results indicate that palmitoylated GPCRs, such as Rh, may acquire raftophilicity upon G protein-stabilized dimerization and thereby organize receptor-cluster rafts by recruiting raftophilic lipids.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2uz4xQJ
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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