title: Dynamin2 controls Rap1 activation and integrin clustering in human T lymphocyte adhesion.
abstract: Leukocyte trafficking is crucial to facilitate efficient immune responses. Here, we report that the large GTPase dynamin2, which is generally considered to have a key role in endocytosis and membrane remodeling, is an essential regulator of integrin-dependent human T lymphocyte adhesion and migration. Chemical inhibition or knockdown of dynamin2 expression significantly reduced integrin-dependent T cell adhesion in vitro. This phenotype was not observed when T cells were treated with various chemical inhibitors which abrogate endocytosis or actin polymerization. We furthermore detected dynamin2 in signaling complexes and propose that it controls T cell adhesion via FAK/Pyk2- and RapGEF1-mediated Rap1 activation. In addition, the dynamin2 inhibitor-induced reduction of lymphocyte adhesion can be rescued by Rap1a overexpression. We demonstrate that the dynamin2 effect on T cell adhesion does not involve integrin affinity regulation but instead relies on its ability to modulate integrin valency. Taken together, we suggest a previously unidentified role of dynamin2 in the regulation of integrin-mediated lymphocyte adhesion via a Rap1 signaling pathway.
authors.affiliation: Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Eppler
authors.affiliation: Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quast
authors.affiliation: Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
authors.forename: Waldemar
authors.identifier: http://orcid.org/0000-0003-1325-9444
authors.initials: W
authors.lastname: Kolanus
mesh_terms: D001692:Biological Transport; D002448:Cell Adhesion; D002465:Cell Movement; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D034285:Dynamin II / Q000378:metabolism*; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D016023:Integrins; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020827:rap1 GTP-Binding Proteins; D034285:Dynamin II