Abstract
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.
Highlights
Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes
To confirm that DHHC7 can directly catalyze the palmitoylation of JAM-C, we examined the S-palmitoylation of JAM-C with co-expression of wild type DHHC7 and a catalytic dead mutant, DHHS7, in which the conserved catalytic cysteine residue is mutated to serine
Because the hydroxylamine cleavage depends on the environment [25], one plausible explanation is the S-palmitoylation in the membrane-proximal region of JAM-C may be shielded from hydroxylamine attack
Summary
Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. 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. The JAM-C expression level in fibrosarcoma and lung cancer cells is reported to be positively correlated to metastasis. We showed that JAM-C undergoes S-palmitoylation on two membrane-proximal cysteine residues (Cys-264 and Cys-265), and this modification can be catalyzed by DHHC7. We found that S-palmitoylation of JAM-C promotes its localization to the cell-cell contact region and regulates cell migration
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