RT Journal Article
SR Electronic
T1 Super-resolution imaging reveals the nanoscale organization of metabotropic glutamate receptors at presynaptic active zones
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaay7193
DO 10.1126/sciadv.aay7193
VO 6
IS 16
A1 Siddig, Sana
A1 Aufmkolk, Sarah
A1 Doose, Sören
A1 Jobin, Marie-Lise
A1 Werner, Christian
A1 Sauer, Markus
A1 Calebiro, Davide
YR 2020
UL http://advances.sciencemag.org/content/6/16/eaay7193.abstract
AB G protein–coupled receptors (GPCRs) play a fundamental role in the modulation of synaptic transmission. A pivotal example is provided by the metabotropic glutamate receptor type 4 (mGluR4), which inhibits glutamate release at presynaptic active zones (AZs). However, how GPCRs are organized within AZs to regulate neurotransmission remains largely unknown. Here, we applied two-color super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) to investigate the nanoscale organization of mGluR4 at parallel fiber AZs in the mouse cerebellum. We find an inhomogeneous distribution, with multiple nanodomains inside AZs, each containing, on average, one to two mGluR4 subunits. Within these nanodomains, mGluR4s are often localized in close proximity to voltage-dependent CaV2.1 channels and Munc-18-1, which are both essential for neurotransmitter release. These findings provide previously unknown insights into the molecular organization of GPCRs at AZs, suggesting a likely implication of a close association between mGluR4 and the secretory machinery in modulating synaptic transmission.