title: S-Palmitoylation of Junctional Adhesion Molecule C Regulates Its Tight Junction Localization and Cell Migration.
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 undergoesS-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-CS-palmitoylation. Moreover, DHHC7 knockdown decreases theS-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 thatS-palmitoylation of JAM-C can be potentially targeted to control cancer metastasis.
authors.affiliation: From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Pornpun
authors.initials: P
authors.lastname: Aramsangtienchai
authors.affiliation: From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Spiegelman
authors.affiliation: From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
authors.affiliation: From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 hl379@cornell.edu.
authors.forename: Hening
authors.identifier: 0000-0002-0255-2701
authors.initials: H
authors.lastname: Lin
mesh_terms: D000072283:A549 Cells; D000123:Acetyltransferases; D000217:Acyltransferases; D002465:Cell Movement / Q000502:physiology*; D003545:Cysteine / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D062786:Junctional Adhesion Molecule C / Q000378:metabolism*; D019169:Jurkat Cells; D054878:Lipoylation / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D062786:Junctional Adhesion Molecule C; D019308:Palmitic Acid; D000217:Acyltransferases; D000123:Acetyltransferases; C447819:ZDHHC7 protein, human; D003545:Cysteine
keywords: cell adhesion; cell migration; chemical biology; post-translational modification (PTM); protein palmitoylation; protein-lipid interaction; tight junction