A Two-state Model for the Diffusion of the A2A Adenosine Receptor in Hippocampal Neurons

Abstract

Background: Agonist activation slows diffusion of the A2A receptor in the lipid bilayer.Results: In hippocampal neurons, the agonist-induced decrease in mobility was accounted for by both the hydrophobic receptor core and its extended C terminus, which recruited SAP102.Conclusion: The observations are consistent with two diffusion states of the A2A receptor in neurons.Significance: SAP102 regulates access of the A2A receptor to a compartment with restricted mobility.

Single Molecule Imaging Deciphers the Relation between Mobility and Signaling of a Prototypical G Protein-coupled Receptor in Living Cells

“…Their general diffusion properties are accessible by other measurement techniques such as fluorescence recovery after photobleaching or fluorescence correlation spectroscopy. The overall features of type I receptors are comparable with those observed by single molecule tracking of other GPCRs (31,(51)(52)(53). The low S MSS values measured here correlate with a restricted diffusion of the NK1R.…”

Subdiffractional tracking of internalized molecules reveals heterogeneous motion states of synaptic vesicles

“…We therefore applied Bayesian model selection to HMMs to investigate the heterogeneous mobility patterns of internalized VAMP2–pHluorin/Atto647N nanobodies in live hippocampal neurons (see Materials and methods). It is common practice to analyze single-particle trajectories with a fixed number of hidden states (Das et al, 2009, 2015; Chung et al, 2010; Thurner et al, 2014; Freeman et al, 2015; Katz et al, 2016). When we assumed a maximum of four hidden states, we found that the optimal number of states was three for almost all presynapses (86%).…”

Diffusion dynamics of synaptic molecules during inhibitory postsynaptic plasticity

“…Free receptor diffusion, with typical diffusion coefficient values of 0.1–1 μm 2 /s, is mainly observed at extrasynaptic compartments, whereas in specialized areas such as synapses, receptor diffusion coefficients can reach even three to four orders of magnitude smaller values, largely due to diffusion traps (Calamai et al, 2009 ; Petrini et al, 2009 ; Muir et al, 2010 ). Indeed, both at inhibitory and excitatory synapses, the interaction of neurotransmitter receptors with scaffold proteins represents the major cause of receptor transient corralling in the postsynaptic area, as in the case of GABA A R-gephyrin (Jacob et al, 2005 ), GlyR-gephyrin (Meier et al, 2001 ), AMPAR-PSD95-stargazin (Bats et al, 2007 ), mGluR-Homer (Sergé et al, 2002 ), D1 receptors-SAP102 (Thurner et al, 2014 ).…”