S-Palmitoylation of Junctional Adhesion Molecule C Regulates Its Tight Junction Localization and Cell Migration [Enzymology]

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, Cys264 and Cys265. We have identified DHHC7 as a JAM-C palmitoylating enzyme by screening all known palmitoyltransferases (PATs or 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.

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