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To promote their trans-endothelial migration (TEM), chemokine receptors control the activity of RHO family small GTPases in part via GTPase-activating proteins (GAPs). T and B cells express several RHO-GAPs, the function of most of which remains unknown. The ARHGAP45 GAP is predominantly expressed in hematopoietic cells. To define its\n                    <jats:italic>in vivo<\/jats:italic>\n                    function, we describe two mouse models where ARHGAP45 is ablated systemically or selectively in T cells. We combine their analysis with affinity purification coupled to mass spectrometry to determine the ARHGAP45 interactome in T cells and with time-lapse and reflection interference contrast microscopy to assess the role of ARGHAP45 in T-cell polarization and motility. We demonstrate that ARHGAP45 regulates na\u00efve T-cell deformability and motility. Under physiological conditions, ARHGAP45 controls the entry of na\u00efve T and B cells into lymph nodes whereas under competitive repopulation it further regulates hematopoietic progenitor cell engraftment in the bone marrow, and T-cell progenitor thymus seeding. Therefore, the ARGHAP45 GAP controls multiple key steps in the life of T and B cells.\n                  <\/jats:p>","DOI":"10.15252\/embr.202052196","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T04:05:34Z","timestamp":1615781134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["ARHGAP45 controls na\u00efve T- and B-cell entry into lymph nodes and T-cell progenitor thymus seeding"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-377X","authenticated-orcid":false,"given":"Le","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-3813","authenticated-orcid":false,"given":"Marie-Pierre","family":"Valignat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7810-9941","authenticated-orcid":false,"given":"Lichen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-0032","authenticated-orcid":false,"given":"Lena","family":"Gelard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-7066","authenticated-orcid":false,"given":"Fanghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Le Guen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-2588","authenticated-orcid":false,"given":"St\u00e9phane","family":"Audebert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-4787","authenticated-orcid":false,"given":"Luc","family":"Camoin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-0327","authenticated-orcid":false,"given":"Even","family":"Fossum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarne","family":"Bogen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Henri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-0552","authenticated-orcid":false,"given":"Romain","family":"Roncagalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-3709","authenticated-orcid":false,"given":"Olivier","family":"Theodoly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-4037","authenticated-orcid":false,"given":"Yinming","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-1445","authenticated-orcid":false,"given":"Marie","family":"Malissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-9342","authenticated-orcid":false,"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"BFEMBR202052196_CR1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.vph.2017.11.007","volume":"101","author":"J Amado-Azevedo","year":"2018","unstructured":"Amado-Azevedo J, Reinhard NR, van Bezu J, van Nieuw Amerongen GP, van Hinsbergh VWM, Hordijk PL (2018) The minor histocompatibility antigen 1 (HMHA1)\/ArhGAP45 is a RacGAP and a novel regulator of endothelial integrity. 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