Kuchynka, O.; Kovalchuk, A.; Nussbaumer, M.; Sviridova, E.; Fessl, T.; Bondar, A.

Heterotrimeric G proteins are key signal transducers in all eukaryotic cells. They are responsible for unification and amplification of perceived extracellular chemical and physical stimuli. Heterotrimeric G proteins are peripheral membrane proteins attached to the inner leaflet of the plasma membrane. Despite numerous available studies, many biophysical aspects regulating G protein signaling, including mobility in the membrane, are insufficiently understood. Here, using single-molecule imaging, we show that different subtypes of heterotrimeric G proteins show high diversity in their mobility in the membrane. We demonstrate that the nature of the G subunit defines the mobility of a heterotrimer. Our results indicate that heterotrimers containing G12 and G13 subunits have remarkably reduced mobility compared to those with Gi/o, Gs, and Gq subunits. These findings identify subtype-specific lateral membrane mobility of G proteins as a factor affecting their signaling dynamics in living cells.