Imperial College London


Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Reader in Cell Biology



+44 (0)20 7594 2128a.hanyaloglu Website




Miss Kiran Dosanjh +44 (0)20 7594 2176




2009Institute of Reproductive and Developmental BiologyHammersmith Campus






BibTex format

author = {Sposini, S and Jean-Alphonse, FG and Ayoub, MA and Oqua, A and West, C and Lavery, S and Brosens, JJ and Reiter, E and Hanyaloglu, AC},
doi = {10.1016/j.celrep.2017.11.023},
journal = {Cell Reports},
pages = {2855--2867},
title = {Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms},
url = {},
volume = {21},
year = {2017}

RIS format (EndNote, RefMan)

AB - 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.
AU - Sposini,S
AU - Jean-Alphonse,FG
AU - Ayoub,MA
AU - Oqua,A
AU - West,C
AU - Lavery,S
AU - Brosens,JJ
AU - Reiter,E
AU - Hanyaloglu,AC
DO - 10.1016/j.celrep.2017.11.023
EP - 2867
PY - 2017///
SN - 2211-1247
SP - 2855
TI - Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms
T2 - Cell Reports
UR -
UR -
VL - 21
ER -