Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. JAM-C has been implicated in leukocyte transendothelial migration, angiogenesis, cell adhesion, cell polarity, spermatogenesis, and metastasis. Here, we show that JAM-C undergoes S-palmitoylation on two juxtamembrane cysteine residues, Cys-264 and Cys-265. We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmitoyltransferases (DHHCs). Ectopic expression of DHHC7, but not a DHHC7 catalytic mutant, enhances JAM-C S-palmitoylation. Moreover, DHHC7 knockdown decreases the S-palmitoylation level of JAM-C. Palmitoylation of JAM-C promotes its localization to tight junctions and inhibits transwell migration of A549 lung cancer cells. These results suggest that S-palmitoylation of JAM-C can be potentially targeted to control cancer metastasis.
Keywords: cell adhesion; cell migration; chemical biology; post-translational modification (PTM); protein palmitoylation; protein-lipid interaction; tight junction.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.