MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival.
MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival.
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DOI：
10.1083/jcb.201304115
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发表时间：
2014-03-03
期刊：
影响因子：
--
通讯作者：
Matter K
中科院分区：
文献类型：
--
作者：
Steed E;Elbediwy A;Vacca B;Dupasquier S;Hemkemeyer SA;Suddason T;Costa AC;Beaudry JB;Zihni C;Gallagher E;Pierreux CE;Balda MS;Matter K
MarvelD 3将MEKK 1募集到紧密连接中，从而下调JNK信号传导，并且对于维持紧密连接的完整性和限制细胞迁移和增殖至关重要。MarvelD 3是紧密连接的跨膜成分，但几乎没有证据表明直接参与连接渗透性屏障。紧密连接还调节引导细胞增殖的信号传导机制;然而，将连接点连接到此类信号传导途径的跨膜组分尚不清楚。在本文中，我们表明，MarvelD 3是一个动态的连接调节MEKK 1-c-Jun氨基末端激酶（JNK）途径。在分化的Caco-2细胞中MarvelD 3表达的缺失导致细胞迁移和增殖增加，而在转移性肿瘤细胞系中的再表达抑制迁移、增殖和体内肿瘤形成。MarvelD 3的表达水平与JNK活性呈负相关，因为MarvelD 3将MEKK 1募集到连接处，导致JNK磷酸化的下调和JNK调节的转录机制的抑制。MarvelD 3内化和JNK活化之间的相互作用调节了渗透压胁迫期间MEKK 1的活化，导致MarvelD 3耗尽细胞中的连接解离和细胞死亡。因此，MarvelD 3将紧密连接与MEKK 1-JNK通路偶联，以调节细胞行为和存活。
MarvelD3 recruits MEKK1 to tight junctions, which down-regulates JNK signaling and is essential for maintaining the integrity of tight junctions and restricting cell migration and proliferation. MarvelD3 is a transmembrane component of tight junctions, but there is little evidence for a direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, the transmembrane components that link the junction to such signaling pathways are not well understood. In this paper, we show that MarvelD3 is a dynamic junctional regulator of the MEKK1–c-Jun NH2-terminal kinase (JNK) pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in increased cell migration and proliferation, whereas reexpression in a metastatic tumor cell line inhibited migration, proliferation, and in vivo tumor formation. Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation and inhibition of JNK-regulated transcriptional mechanisms. Interplay between MarvelD3 internalization and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissociation and cell death in MarvelD3-depleted cells. MarvelD3 thus couples tight junctions to the MEKK1–JNK pathway to regulate cell behavior and survival.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
DOI：
10.1083/jcb.200510043
发表时间：
2005-12-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ikenouchi J;Furuse M;Furuse K;Sasaki H;Tsukita S;Tsukita S
通讯作者：
Tsukita S
影响因子：
11.4
作者：
Frankel, P;Aronheim, A;Marshall, CJ
通讯作者：
Marshall, CJ
影响因子：
4
作者：
Kavanagh, Emma;Buchert, Michael;Matter, Karl
通讯作者：
Matter, Karl
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K