Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration
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 un...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02001/full |
| id |
doaj-8a574cb581224a63a5b7c9b17f9d3650 |
|---|---|
| record_format |
Article |
| spelling |
doaj-8a574cb581224a63a5b7c9b17f9d36502020-11-25T00:31:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02001389082Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell MigrationLaura Megrelis0Laura Megrelis1Laura Megrelis2Elyas El Ghoul3Elyas El Ghoul4Elyas El Ghoul5Federica Moalli6Margaux Versapuech7Margaux Versapuech8Margaux Versapuech9Shamir Cassim10Shamir Cassim11Shamir Cassim12Nora Ruef13Jens V. Stein14Marianne Mangeney15Marianne Mangeney16Marianne Mangeney17Jérôme Delon18Jérôme Delon19Jérôme Delon20Infection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceInfection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceTheodor Kocher Institute, University of Bern, Bern, SwitzerlandInfection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceInfection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandInfection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceInfection, Immunity, Inflammation, Inserm, U1016, Institut Cochin, Paris, FranceCNRS, UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cité, Paris, FranceWe 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02001/fullRho GTPasesT cell migrationchemokine signalingmouse modelphosphoproteins |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Laura Megrelis Laura Megrelis Laura Megrelis Elyas El Ghoul Elyas El Ghoul Elyas El Ghoul Federica Moalli Margaux Versapuech Margaux Versapuech Margaux Versapuech Shamir Cassim Shamir Cassim Shamir Cassim Nora Ruef Jens V. Stein Marianne Mangeney Marianne Mangeney Marianne Mangeney Jérôme Delon Jérôme Delon Jérôme Delon |
| spellingShingle |
Laura Megrelis Laura Megrelis Laura Megrelis Elyas El Ghoul Elyas El Ghoul Elyas El Ghoul Federica Moalli Margaux Versapuech Margaux Versapuech Margaux Versapuech Shamir Cassim Shamir Cassim Shamir Cassim Nora Ruef Jens V. Stein Marianne Mangeney Marianne Mangeney Marianne Mangeney Jérôme Delon Jérôme Delon Jérôme Delon Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration Frontiers in Immunology Rho GTPases T cell migration chemokine signaling mouse model phosphoproteins |
| author_facet |
Laura Megrelis Laura Megrelis Laura Megrelis Elyas El Ghoul Elyas El Ghoul Elyas El Ghoul Federica Moalli Margaux Versapuech Margaux Versapuech Margaux Versapuech Shamir Cassim Shamir Cassim Shamir Cassim Nora Ruef Jens V. Stein Marianne Mangeney Marianne Mangeney Marianne Mangeney Jérôme Delon Jérôme Delon Jérôme Delon |
| author_sort |
Laura Megrelis |
| title |
Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration |
| title_short |
Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration |
| title_full |
Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration |
| title_fullStr |
Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration |
| title_full_unstemmed |
Fam65b Phosphorylation Relieves Tonic RhoA Inhibition During T Cell Migration |
| title_sort |
fam65b phosphorylation relieves tonic rhoa inhibition during t cell migration |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2018-09-01 |
| description |
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. |
| topic |
Rho GTPases T cell migration chemokine signaling mouse model phosphoproteins |
| url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02001/full |
| work_keys_str_mv |
AT lauramegrelis fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT lauramegrelis fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT lauramegrelis fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT elyaselghoul fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT elyaselghoul fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT elyaselghoul fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT federicamoalli fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT margauxversapuech fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT margauxversapuech fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT margauxversapuech fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT shamircassim fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT shamircassim fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT shamircassim fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT noraruef fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT jensvstein fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT mariannemangeney fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT mariannemangeney fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT mariannemangeney fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT jeromedelon fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT jeromedelon fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration AT jeromedelon fam65bphosphorylationrelievestonicrhoainhibitionduringtcellmigration |
| _version_ |
1725321992253472768 |