RT Journal Article
SR Electronic
T1 Subsynaptic mobility of presynaptic mGluR types is differentially regulated by intra- and extracellular interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.06.188995
DO 10.1101/2020.07.06.188995
A1 Bodzęta, Anna
A1 Berger, Florian
A1 MacGillavry, Harold D.
YR 2021
UL http://biorxiv.org/content/early/2021/04/02/2020.07.06.188995.abstract
AB Presynaptic metabotropic glutamate receptors (mGluRs) are essential for activity-dependent modulation of synaptic transmission. However, the mechanisms that control the subsynaptic dynamics of these receptors and their contribution to synaptic signaling are poorly understood. Here, using complementary super-resolution microscopy and single-molecule tracking techniques, we provide novel insights into the molecular mechanisms that control the nanoscale distribution and mobility of presynaptic mGluRs in hippocampal neurons. We demonstrate that the group II receptor mGluR2 localizes diffusely along the axon and boutons, and is highly mobile, while the group III receptor mGluR7 is stably anchored at the active zone, indicating that distinct mechanisms underlie the dynamic distribution of these receptor types. Surprisingly, using domain swapping experiments we found that intracellular interactions modulate surface diffusion of mGluR2, but not mGluR7. Instead, we found that immobilization of mGluR7 at the active zone relies on its extracellular domain. Importantly, receptor activation or increase in synaptic activity did not alter the surface mobility of presynaptic mGluRs. Finally, computational modeling of presynaptic mGluR activity revealed that the precise subsynaptic distribution of mGluRs controls their activation probability and thus directly impacts their ability to modulate neurotransmitter release. Altogether, this study demonstrates that distinct mechanisms control surface mobility of presynaptic mGluRs to differentially contribute to the regulation of glutamatergic synaptic transmission.Competing Interest StatementThe authors have declared no competing interest.