Potentiation of receptor responses induced by prolonged binding of Gα 13 and leukemia‐associated RhoGEF

Diverse cellular functions are controlled by RhoA‐GTPases, which are activated by trimeric G proteins via RhoGEFs, among others. In this study, we focused on the signaling from GPCRs to RhoA via Ga 13 and leukemia‐associated RhoGEF (LARG). The activation of Ga 13 was elucidated in living cells with high temporal and spatial resolution by means of FRET. The inactivation after agonist withdrawal occurred in the same range (t 1/2 = 25.3 6 2.2 s; mean 6 SEM; n = 22) as described for other Ga proteins. The interaction of Ga 13 and LARG and the thereby‐induced LARG translocation to the plasma membrane were at least 1 order of magnitude more stable after agonist withdrawal, exceeding Ga 13 deactivation in the absence of LARG several fold. Consequently, we observed an almost 100‐fold higher agonist sensitivity of the Ga 13 LARG interaction compared to the Ga 13 activation in the absence of LARG.—Bodmann, E.‐L., Krett, A.‐L., Bünemann, M. Potentiation of receptor responses induced by prolonged binding of Ga 13 and leukemia‐associated RhoGEF. FASEB J . 31, 3663–3676 (2017). www.fasebj.org