10.3389/fimmu.2018.02001.s001
Laura Megrelis
Laura
Megrelis
Elyas El Ghoul
Elyas El
Ghoul
Federica Moalli
Federica
Moalli
Margaux Versapuech
Margaux
Versapuech
Shamir Cassim
Shamir
Cassim
Nora Ruef
Nora
Ruef
Jens V. Stein
Jens V.
Stein
Marianne Mangeney
Marianne
Mangeney
Jérôme Delon
Jérôme
Delon
Image_1_Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration.tif
Frontiers
2018
Rho GTPases
T cell migration
chemokine signaling
mouse model
phosphoproteins
2018-09-11 04:28:03
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_Fam65b_Phosphorylation_Relieves_Tonic_RhoA_Inhibition_During_T_Cell_Migration_tif/7070960
<p>We previously identified Fam65b as an atypical inhibitor of the small G protein RhoA. Using a conditional model of a Fam65b-deficient mouse, we first show that Fam65b restricts spontaneous RhoA activation in resting T lymphocytes and regulates intranodal T cell migration in vivo. We next aimed at understanding, at the molecular level, how the brake that Fam65b exerts on RhoA can be relieved upon signaling to allow RhoA activation. Here, we show that chemokine stimulation phosphorylates Fam65b in T lymphocytes. This post-translational modification decreases the affinity of Fam65b for RhoA and favors Fam65b shuttling from the plasma membrane to the cytosol. Functionally, we show that the degree of Fam65b phosphorylation controls some cytoskeletal alterations downstream active RhoA such as actin polymerization, as well as T cell migration in vitro. Altogether, our results show that Fam65b expression and phosphorylation can finely tune the amount of active RhoA in order to favor optimal T lymphocyte motility.</p>