Sodium channel β subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact
Sodium channel β subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact
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DOI：
10.1074/jbc.275.15.11383
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发表时间：
2000-04-14
影响因子：
4.8
通讯作者：
Isom, LL
中科院分区：
文献类型：
--
作者：
Malhotra, JD;Kazen-Gillespie, K;Isom, LL
从哺乳动物脑中分离的钠通道由α、β1和β2亚基组成，辅助的β亚基不形成离子传导孔，但在通道调制和质膜表达中起重要作用，β1和β2是跨膜蛋白，具有一个细胞外V集免疫球蛋白(Ig)蛋白结构域。最近的研究表明，β1和β2与细胞外基质蛋白tenascin-C和tenascin-R相互作用，在本研究中，我们发现大鼠脑内的β1和β2亚基相互作用，而不是αIIA亚基，导致细胞骨架蛋白ankyrin在转基因果蝇S2细胞中的细胞-细胞接触部位重新募集。虽然单独表达的αIIA亚基不会引起细胞聚集，但与αIIA共表达的β亚基保留了黏附和募集Ankyrin的能力，缺少胞浆结构域的截短的Beta亚基可以同亲作用产生细胞聚集，但不招募Ankyrin，因此，细胞骨架相互作用需要β1和β2的胞质结构域。推测钠通道β亚基在神经元的胞外和胞内环境之间起着重要的通讯纽带作用，并可能在兰维尔结节的钠通道定位中发挥作用。
Sodium channels isolated from mammalian brain are composed of alpha, beta 1, and beta 2 subunits, The auxiliary beta subunits do not form the ion conducting pore, yet play important roles in channel modulation and plasma membrane expression, beta 1 and beta 2 are transmembrane proteins with one extracellular V-set immunoglobulin (Ig) protein domain. It has been shown recently that beta 1 and beta 2 interact with the extracellular matrix proteins tenascin-C and tenascin-R, In the present study we show that rat brain beta 1 and beta 2, but not alpha IIA, subunits interact in a trans-homophilic fashion, resulting in recruitment of the cytoskeletal protein ankyrin to sites of cell-cell contact in transfected Drosophila S2 cells. Whereas alpha IIA subunits expressed alone do not cause cellular aggregation, beta subunits co-expressed with alpha IIA retain the ability to adhere and recruit ankyrin, Truncated beta subunits lacking cytoplasmic domains interact homophilically to produce cell aggregation but do not recruit ankyrin, Thus, the cytoplasmic domains of beta 1 and beta 2 are required for cytoskeletal interactions. It is hypothesized that sodium channel beta subunits serve as a critical communication link between the extracellular and intracellular environments of the neuron and may play a role in sodium channel placement at nodes of Ranvier.