Canna~Fangled Abstracts

Retromer stops beta-arrestin 1 mediated signaling from internalized cannabinoid 2 receptors.

By September 27, 2017 No Comments
Mol Biol Cell. 2017 Sep 27. pii: mbc.E17-03-0198. doi: 10.1091/mbc.E17-03-0198.
[Epub ahead of print]


PM 2 site 207G protein-coupled receptors (GPCRs) mediate their complex functions through activation of signaling cascades from receptors localized at the cell surface and endosomal compartments. These signaling pathways are modulated by heterotrimeric G proteins and the scaffold proteins beta-arrestin 1 and 2. However, in contrast to the events occurring at the cell surface, our knowledge of the mechanisms controlling signaling from receptors localized at intracellular compartments is still very limited. Here, we sought to investigate the intracellular signaling from cannabinoid 2 receptor (CB2R). First, we show that receptor internalization is required for agonist induced phosphorylation of ERK1/2. Then, we demonstrate that ERK1/2 activation is mediated by beta-arrestin 1 from receptors localized exclusively at Rab4/5 compartments. Finally, we identify the retromer complex as a gatekeeper, terminating beta-arrestin 1 mediated ERK phosphorylation. These findings extend our understanding of the events controlling signaling from endocytosed receptors and identify the retromer as a modulator of beta-arrestin mediated signaling from CB2R.

PMID: 28954865


DOI: 10.1091/mbc.E17-03-0198
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