- 连接粘附分子C的棕榈酰化调节其紧密连接定位和细胞迁移。
-Palmitoylation of Junctional Adhesion Molecule C Regulates Its Tight Junction Localization and Cell Migration.
作者信息
Aramsangtienchai Pornpun, Spiegelman Nicole A, Cao Ji, Lin Hening
机构信息
From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
From the Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853
出版信息
J Biol Chem. 2017 Mar 31;292(13):5325-5334. doi: 10.1074/jbc.M116.730523. Epub 2017 Feb 14.
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 -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 -palmitoylation. Moreover, DHHC7 knockdown decreases the -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 -palmitoylation of JAM-C can be potentially targeted to control cancer metastasis.
摘要
连接黏附分子C（JAM-C）是一种免疫球蛋白超家族蛋白，在上皮细胞、内皮细胞和白细胞中表达。JAM-C与白细胞跨内皮迁移、血管生成、细胞黏附、细胞极性、精子发生和转移有关。在此，我们表明JAM-C在两个近膜半胱氨酸残基Cys-264和Cys-265上发生棕榈酰化。通过筛选所有已知的棕榈酰转移酶（DHHCs），我们确定DHHC7是一种JAM-C棕榈酰化酶。异位表达DHHC7而非DHHC7催化突变体可增强JAM-C的棕榈酰化。此外，敲低DHHC7可降低JAM-C的棕榈酰化水平。JAM-C的棕榈酰化促进其定位于紧密连接，并抑制A549肺癌细胞的Transwell迁移。这些结果表明，JAM-C的棕榈酰化可能是控制癌症转移的潜在靶点。
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