--- res: bibo_abstract: - RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency also resulted in defective proliferation, activation and motility of T cells and B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity with defective granule convergence and actin accumulation. Interaction proteomics identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed the migration and activation defects of RASGRP1-deficient lymphocytes.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Elisabeth foaf_name: Salzer, Elisabeth foaf_surname: Salzer - foaf_Person: foaf_givenName: Deniz foaf_name: Çaǧdaş, Deniz foaf_surname: Çaǧdaş - foaf_Person: foaf_givenName: Miroslav foaf_name: Hons, Miroslav foaf_surname: Hons foaf_workInfoHomepage: http://www.librecat.org/personId=4167FE56-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6625-3348 - foaf_Person: foaf_givenName: Emily foaf_name: Mace, Emily foaf_surname: Mace - foaf_Person: foaf_givenName: Wojciech foaf_name: Garncarz, Wojciech foaf_surname: Garncarz - foaf_Person: foaf_givenName: Oezlem foaf_name: Petronczki, Oezlem foaf_surname: Petronczki - foaf_Person: foaf_givenName: René foaf_name: Platzer, René foaf_surname: Platzer - foaf_Person: foaf_givenName: Laurène foaf_name: Pfajfer, Laurène foaf_surname: Pfajfer - foaf_Person: foaf_givenName: Ivan foaf_name: Bilic, Ivan foaf_surname: Bilic - foaf_Person: foaf_givenName: Sol foaf_name: Ban, Sol foaf_surname: Ban - foaf_Person: foaf_givenName: Katharina foaf_name: Willmann, Katharina foaf_surname: Willmann - foaf_Person: foaf_givenName: Malini foaf_name: Mukherjee, Malini foaf_surname: Mukherjee - foaf_Person: foaf_givenName: Verena foaf_name: Supper, Verena foaf_surname: Supper - foaf_Person: foaf_givenName: Hsiangting foaf_name: Hsu, Hsiangting foaf_surname: Hsu - foaf_Person: foaf_givenName: Pinaki foaf_name: Banerjee, Pinaki foaf_surname: Banerjee - foaf_Person: foaf_givenName: Papiya foaf_name: Sinha, Papiya foaf_surname: Sinha - foaf_Person: foaf_givenName: Fabienne foaf_name: Mcclanahan, Fabienne foaf_surname: Mcclanahan - foaf_Person: foaf_givenName: Gerhard foaf_name: Zlabinger, Gerhard foaf_surname: Zlabinger - foaf_Person: foaf_givenName: Winfried foaf_name: Pickl, Winfried foaf_surname: Pickl - foaf_Person: foaf_givenName: John foaf_name: Gribben, John foaf_surname: Gribben - foaf_Person: foaf_givenName: Hannes foaf_name: Stockinger, Hannes foaf_surname: Stockinger - foaf_Person: foaf_givenName: Keiryn foaf_name: Bennett, Keiryn foaf_surname: Bennett - foaf_Person: foaf_givenName: Johannes foaf_name: Huppa, Johannes foaf_surname: Huppa - foaf_Person: foaf_givenName: Loï̈C foaf_name: Dupré, Loï̈C foaf_surname: Dupré - foaf_Person: foaf_givenName: Özden foaf_name: Sanal, Özden foaf_surname: Sanal - foaf_Person: foaf_givenName: Ulrich foaf_name: Jäger, Ulrich foaf_surname: Jäger - foaf_Person: foaf_givenName: Michael K foaf_name: Sixt, Michael K foaf_surname: Sixt foaf_workInfoHomepage: http://www.librecat.org/personId=41E9FBEA-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6620-9179 - foaf_Person: foaf_givenName: Ilhan foaf_name: Tezcan, Ilhan foaf_surname: Tezcan - foaf_Person: foaf_givenName: Jordan foaf_name: Orange, Jordan foaf_surname: Orange - foaf_Person: foaf_givenName: Kaan foaf_name: Boztug, Kaan foaf_surname: Boztug bibo_doi: 10.1038/ni.3575 bibo_issue: '12' bibo_volume: 17 dct_date: 2016^xs_gYear dct_language: eng dct_publisher: Nature Publishing Group@ dct_title: RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics@ fabio_hasPubmedId: '27776107' ...