期刊
MOLECULAR BIOLOGY OF THE CELL
卷 25, 期 10, 页码 1574-1585出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E14-01-0018
关键词
-
类别
资金
- National Institutes of Health [DK061379, DK072564, K079392, DK59888, DK55679, DK064399]
- Public Health Service [T32 GM007347, F31 NS074596, R01 AI76983]
- German Research Foundation [KFO-274, R37 AI38296]
- Elizabeth B. Lamb Center for Pediatric Research
- Vanderbilt-Ingram Cancer Center [CA68485]
- Vanderbilt Flow Cytometry Shared Resource [DK058404]
- Vanderbilt Cell Imaging Shared Resource [DK20593]
Junctional adhesion molecule-A (JAM-A) is a tight junction-associated signaling protein that regulates epithelial cell proliferation, migration, and barrier function. JAM-A dimerization on a common cell surface (in cis) has been shown to regulate cell migration, and evidence suggests that JAM-A may form homodimers between cells (in trans). Indeed, transfection experiments revealed accumulation of JAM-A at sites between transfected cells, which was lost in cells expressing cis-or predicted trans-dimerization null mutants. Of importance, microspheres coated with JAM-A containing alanine substitutions to residues 43NNP45 (NNP-JAM-A) within the predicted trans-dimerization site did not aggregate. In contrast, beads coated with cis-null JAM-A demonstrated enhanced clustering similar to that observed with wild-type (WT) JAM-A. In addition, atomic force microscopy revealed decreased association forces in NNP-JAM-A compared with WT and cis-null JAM-A. Assessment of effects of JAM-A dimerization on cell signaling revealed that expression of trans-but not cis-null JAM-A mutants decreased Rap2 activity. Furthermore, confluent cells, which enable trans-dimerization, had enhanced Rap2 activity. Taken together, these results suggest that trans-dimerization of JAM-A occurs at a unique site and with different affinity compared with dimerization in cis. Trans-dimerization of JAM-A may thus act as a barrier-inducing molecular switch that is activated when cells become confluent.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据