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Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms
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Sposini, Silvia, Jean-Alphonse, Frederic G., Ayoub, Mohammed A., Oqua, Affiong, West, Camilla, Lavery, Stuart, Brosens, Jan J., Reiter, Eric and Hanyaloglu, Aylin C. (2017) Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms. Cell Reports, 21 (10). pp. 2855-2867. doi:10.1016/j.celrep.2017.11.023
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WRAP-integration-GPCR-signaling-sorting-early-endosomes-Brosens-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2882Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.celrep.2017.11.023
Abstract
Endocytic trafficking is a critical mechanism for cells to decode complex signaling pathways, including those activated by G-protein-coupled receptors (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be spatially restricted between early endosomes (EEs) and the recently discovered endosomal compartment, the very early endosome (VEE). However, the molecular machinery driving GPCR activity from the VEE is unknown. Using luteinizing hormone receptor (LHR) as a prototype GPCR for this compartment, along with additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1 in rapid recycling and endosomal cAMP signaling without impacting the EE-localized β2-adrenergic receptor. LHR recycling is driven by receptor-mediated Gαs/cAMP signaling from the VEE and PKA-dependent phosphorylation of APPL1 at serine 410. Receptor/Gαs endosomal signaling is localized to microdomains of heterogeneous VEE populations and regulated by APPL1 phosphorylation. Our study uncovers a highly integrated inter-endosomal communication system enabling cells to tightly regulate spatially encoded signaling.
| Item Type: | Journal Article | |||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology | |||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Luteinizing hormone -- Receptors, Endosomes, Cell receptors | |||||||||||||||||||||
| Journal or Publication Title: | Cell Reports | |||||||||||||||||||||
| Publisher: | Elsevier Inc. | |||||||||||||||||||||
| ISSN: | 2211-1247 | |||||||||||||||||||||
| Official Date: | 5 December 2017 | |||||||||||||||||||||
| Dates: |
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| Volume: | 21 | |||||||||||||||||||||
| Number: | 10 | |||||||||||||||||||||
| Page Range: | pp. 2855-2867 | |||||||||||||||||||||
| DOI: | 10.1016/j.celrep.2017.11.023 | |||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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