Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration.

Megrelis, Laura; El Ghoul, Elyas; Moalli, Federica; Versapuech, Margaux; Cassim, Shamir; Ruef, Nora Maria; Stein, Jens Volker; Mangeney, Marianne; Delon, Jérôme (2018). Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration. Frontiers in immunology, 9, p. 2001. Frontiers Research Foundation 10.3389/fimmu.2018.02001

[img]
Preview
Text
fimmu-09-02001.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

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 . 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 . 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Moalli, Federica; Ruef, Nora Maria and Stein, Jens Volker

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

12 Feb 2019 12:39

Last Modified:

23 Oct 2019 02:53

Publisher DOI:

10.3389/fimmu.2018.02001

PubMed ID:

30254631

Uncontrolled Keywords:

Rho GTPases T cell migration chemokine signaling mouse model phosphoproteins

BORIS DOI:

10.7892/boris.124118

URI:

https://boris.unibe.ch/id/eprint/124118

Actions (login required)

Edit item Edit item
Provide Feedback