Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane

Marie-Lise Jobin*, Sana Siddig, Zsombor Koszegi, Yann Lanoiselée, Vladimir Khayenko, Titiwat Sungkaworn, Christian Werner, Kerstin Seier, Christin Misigaiski, Giovanna Mantovani, Markus Sauer, Hans M. Maric, Davide Calebiro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

The γ-aminobutyric acid type B (GABAB) receptor is a prototypical family C G protein-coupled receptor (GPCR) that plays a key role in the regulation of synaptic transmission. Although growing evidence suggests that GPCR signaling in neurons might be highly organized in time and space, limited information is available about the mechanisms controlling the nanoscale organization of GABAB receptors and other GPCRs on the neuronal plasma membrane. Using a combination of biochemical assays in vitro, single-particle tracking, and super-resolution microscopy, we provide evidence that the spatial organization and diffusion of GABAB receptors on the plasma membrane are governed by dynamic interactions with filamin A, which tethers the receptors to sub-cortical actin filaments. We further show that GABAB receptors are located together with filamin A in small nanodomains in hippocampal neurons. These interactions are mediated by the first intracellular loop of the GABAB1 subunit and modulate the kinetics of Gαi protein activation in response to GABA stimulation.
Original languageEnglish
Article number34
Number of pages14
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 3 Jan 2023

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