Interleukin‐16 Signaling Through the CD9 Receptor Initates Rearrangement of the Actin Cytoskeleton

Abstract

CD9 is a tetraspanin membrane protein that plays critical roles in various cellular processes including cellular proliferation, activation, intracellular signaling, survival, invasion, migration, cell adhesion, and cytoskeletal rearrangement. All major subsets of leukocytes, as well as some endothelial cells, express the CD9 receptor. Activation of CD9 occurs through interactions with a variety of cell surface molecules including integrins and other adhesion molecules. Recent evidence has indicated that the cytokine, Interleukin‐16 (IL‐16), can also serve as a ligand for activation of the CD9 receptor. IL‐16 is best known as an immunomodulatory, pro‐inflammatory cytokine that aids in CD4+ cell recruitment and stimulation at sites of inflammation through signaling via the CD4 receptor. However, CD9 has been implicated as an alternative receptor in several cell types lacking the CD4 receptor. For example, recent studies have established that cells deficient in CD4 are reactive to IL‐16 including increased cytokine production, cell migration, and neural outgrowth. Recently, we showed that in a human lung cancer epithelium cell line (A549 cells), CD9 is required for cell migration specifically towards IL‐16 providing compelling evidence that CD9 is an alternate receptor for IL‐16. In this study, we used A549 cells either expressing CD9 (CD9+) or lacking CD9 (CD9−) due to genetic ablation via CRISPR/Cas technology to examine the effects on cytoskeletal rearrangement upon activation following incubation with recombinant IL‐16. Our preliminary evidence indicates that in A549 cells, IL‐16 treatment initiates robust rearrangement of both the actin cytoskeleton and associated proteins such as vinculin and talin. Further studies will examine the differences in IL‐16‐mediated cytoskeleton reorganization between CD9+ and CD9− cells.Support or Funding InformationNIH‐MARC U*STAR award number T34GM092711BLaST Undergraduate Research ExperienceCO‐WYAMP of NSF LSAMP: Mini‐grant