Venue : Centre Broca Nouvelle-Aquitaine, conference room
Damien Jullié, PhD
Department of Cellular and Molecular Pharmacology and Department of Psychiatry,
University of California, San Francisco School of Medicine
Invited by: David Perrais
A major function of GPCRs is to inhibit neurotransmitter release from presynaptic terminals. This requires ligand-activated receptors to couple locally to effectors at terminals. The current understanding of how this is achieved is based on receptor immobilization on the presynaptic surface. Here we show that opioid peptide receptors, GPCRs which mediate highly sensitive presynaptic inhibition, are instead dynamic in axons. Opioid receptors diffuse rapidly throughout the axon surface and internalize after ligand-induced activation specifically at presynaptic terminals. We delineate a parallel regulated endocytic cycle for GPCRs at the presynapse, separate from the synaptic vesicle cycle, which clears activated receptors from the presynaptic surface and mediates local reinsertion to maintain the diffusible surface pool. We propose an alternate strategy to achieve local control of presynaptic effectors that, opposite to being based on receptor immobilization, is based on lateral mobility of receptors and leverages the inherently allosteric nature of GPCR – effector coupling.
Stoeber M, Jullié D, Lobingier BT, Laeremans T, Steyaert J, Schiller PW, Manglik A, von Zastrow M. A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action. Neuron. 2018 Jun 6;98(5):963-976.
Eichel K, Jullié D, Barsi-Rhyne B, Latorraca NR, Masureel M, Sibarita JB, Dror RO, von Zastrow M. Catalytic activation of β-arrestin by GPCRs. Nature. 2018 May;557(7705):381-386.
Rosendale M, Jullié D, Choquet D, Perrais D. Spatial and Temporal Regulation of Receptor Endocytosis in Neuronal Dendrites Revealed by Imaging of Single Vesicle Formation. Cell Rep. 2017 Feb 21;18(8):1840-1847.
Jullié D, Choquet D, Perrais D. Recycling endosomes undergo rapid closure of a fusion pore on exocytosis in neuronal dendrites. J Neurosci. 2014 Aug 13;34(33):11106-18.