The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)
The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)
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DOI：
10.1093/emboj/20.14.3738
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发表时间：
2001-07-16
期刊：
影响因子：
11.4
通讯作者：
Vestweber, D
中科院分区：
文献类型：
--
作者：
Ebnet, K;Suzuki, A;Vestweber, D
细胞极性的建立和维持对于多细胞生物的发育至关重要。PAR（partitioning-deficient）蛋白在秀丽隐杆线虫中被鉴定为不对称细胞分裂和极化细胞生长的决定因素。最近，脊椎动物的直向同源物的两个这些蛋白质，ASIP/PAR-3和PAR-6，被发现形成一个信号复合物与小GTP酶Cdc 42/Rac 1和非典型蛋白激酶C（PKC）。在这里，我们表明，ASIP/PAR-3协会与紧密连接相关蛋白连接粘附分子（JAM）在体外和体内。未观察到与密蛋白-1、密蛋白-4或密蛋白-5的结合。在过表达JAM的成纤维细胞和CHO细胞中，内源性ASIP在细胞-细胞接触位点被募集至JAM。缺乏胞外部分的截短的JAM的过表达破坏了ASIP/PAR-3在细胞间连接处的定位，并延迟了ASIP/PAR-3向新形成的细胞连接的募集。在连接形成过程中，JAM在连接的原始形式中出现较早。我们的数据表明，ASIP/PAR-3-aPKC复合物通过其与JAM的关联被拴系到紧密连接，表明JAM在上皮细胞中细胞极性的产生中的潜在作用。
The establishment and maintenance of cellular polarity are critical for the development of multicellular organisms. PAR (partitioning-defective) proteins were identified in Caenorhabditis elegans as determinants of asymmetric cell division and polarized cell growth. Recently, vertebrate orthologues of two of these proteins, ASIP/PAR-3 and PAR-6, were found to form a signalling complex with the small GTPases Cdc42/Rac1 and with atypical protein kinase C (PKC). Here we show that ASIP/PAR-3 associates with the tight-junction-associated protein junctional adhesion molecule (JAM) in vitro and in vivo. No binding was observed with claudin-1, -4 or -5. In fibroblasts and CHO cells overexpressing JAM, endogenous ASIP is recruited to JAM at sites of cell-cell contact. Overexpression of truncated JAM lacking the extracellular part disrupts ASIP/PAR-3 localization at intercellular junctions and delays ASIP/PAR-3 recruitment to newly formed cell junctions. During junction formation, JAM appears early in primordial forms of junctions. Our data suggest that the ASIP/PAR-3-aPKC complex is tethered to tight junctions via its association with JAM, indicating a potential role for JAM in the generation of cell polarity in epithelial cells.