title: The activity of aminoacyl-tRNA synthetase-interacting multi-functional protein 1 (AIMP1) on endothelial cells is mediated by the assembly of a cytoskeletal protein complex.
abstract: AIMP1 was first found as a factor associated with the aminoacyl-tRNA synthetase (ARS) complex. However, it is also secreted and acts on different target cells such as endothelial cells, macrophages, and fibroblasts as an extracellular regulator, respectively, of angiogenesis, inflammatory responses and dermal regeneration. AIMP1 has also been reported to suppress in vivo tumor growth. In this study, we investigated the signaling pathways activated by exogenous AIMP1 in an in vitro endothelial model. AIMP1 decreases EC viability through an α5β1 integrin-dependent mechanism and inhibits cell adhesion, is internalized and shows an asymmetric pattern of distribution and accumulation in cell protrusions. Experiments of affinity purification, pull down, and co-immunoprecipitation showed that AIMP1 interacts with four cytoskeletal proteins (filamin-A, α-tubulin, vinculin, and cingulin). α-Tubulin also gets phosphorylated upon cell treatment with AIMP1 and colocalization between AIMP1 and filamin-A as well as between AIMP1 and cingulin was observed through immunofluorescence assays. In this work, we propose that AIMP1 effect on EC adhesion is mediated by the assembly of a cytoskeletal protein complex on the cytosolic face of the cell membrane which could regulate cellular architecture maintenance and remodeling. Moreover, this activity is able to indirectly influence cell viability.
authors.affiliation: LIMA, BioIndustry Park Silvano Fumero S.p.A., Colleretto Giacosa (TO), Italy. jackson@bipcamail.it
authors.forename: Valentina Charlotte
authors.initials: VC
authors.lastname: Jackson
authors.forename: Sarah
authors.initials: S
authors.lastname: Dewilde
authors.forename: Alessandra Giuliano
authors.initials: AG
authors.lastname: Albo
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lis
authors.forename: Davide
authors.initials: D
authors.lastname: Corpillo
authors.forename: Barbara
authors.initials: B
authors.lastname: Canepa
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003285:Contractile Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D064448:Filamins; D006801:Humans; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D014404:Tubulin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D016207:Cytokines; D003598:Cytoskeletal Proteins; D064448:Filamins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014404:Tubulin; C077219:small inducible cytokine subfamily E, member 1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases