Multiple Kv1.5 targeting to membrane surface microdomains.
Multiple Kv1.5 targeting to membrane surface microdomains.
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DOI：
10.1002/jcp.21538
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发表时间：
2008-12
影响因子：
5.6
通讯作者：
Felipe, Antonio
中科院分区：
文献类型：
--
作者：
Martinez-Marmol, Ramon;Villalonga, Nuria;Sole, Laura;Vicente, Ruben;Tamkun, Michael M.;Soler, Concepcio;Felipe, Antonio
电压依赖性K+通道（Kv）的表面表达在白细胞生理学中具有关键作用。虽然对脂筏的生理作用知之甚少，但这些微区集中了信号分子及其离子通道底物。Kv1.3与Kv1.5结合形成巨噬细胞中的功能通道。不同的同种型化学计量导致不同的异源通道，其可以通过将复合物靶向不同的膜表面微区来进一步调节。Kv1.3靶向脂筏，而Kv1.5定位仍有争议。考虑到这一点，我们想研究是否异源四聚体Kv1.5含有通道靶向脂筏。而在转染的HEK-293细胞中，同源和异源四聚体通道靶向筏，Kv1.5不靶向巨噬细胞中的筏。因此，Kv1.3/Kv1.5混合通道主要集中在非筏微区。然而，脂多糖诱导的激活增加了Kv1.3/Kv1.5比率和小窝蛋白，将Kv1.5靶向回到脂筏。此外，Kv1.5没有本地化的L 6 E9骨骼肌成肌细胞，这也共表达两个通道，心脏膜或心肌细胞的低浮力部分。Cav 3DGV突变体的共表达将Kv1.5限制在HEK细胞的Cav 3DGV囊泡中。相反，Kvβ2.1的共表达削弱了Kv 1.5在HEK细胞中对筏微结构域的靶向。我们的研究结果表明，Kv1.5伙伴关系的相互作用是潜在的机制，管理通道靶向脂筏。
Surface expression of voltage-dependent K+ channels (Kv) has a pivotal role in leukocyte physiology. Although little is known about the physiological role of lipid rafts, these microdomains concentrate signaling molecules and their ion channel substrates. Kv1.3 associates with Kv1.5 to form functional channels in macrophages. Different isoform stoichiometries lead to distinct heteromeric channels which may be further modulated by targeting the complex to different membrane surface microdomains. Kv1.3 targets to lipid rafts, whereas Kv1.5 localization is under debate. With this in mind, we wanted to study whether heterotetrameric Kv1.5-containing channels target to lipid rafts. While in transfected HEK-293 cells, homo- and heterotetrameric channels targeted to rafts, Kv1.5 did not target to rafts in macrophages. Therefore, Kv1.3/Kv1.5 hybrid channels are mostly concentrated in non-raft microdomains. However, LPS-induced activation, which increases the Kv1.3/Kv1.5 ratio and caveolin, targeted Kv1.5 back to lipid rafts. Moreover, Kv1.5 did not localize to low-buoyancy fractions in L6E9 skeletal myoblasts, which also coexpress both channels, heart membranes or cardiomyocyes. Coexpression of a Cav3DGV-mutant confined Kv1.5 to Cav3DGV-vesicles of HEK cells. Contrarily, coexpression of Kvβ2.1 impaired the Kv1.5 targeting to raft microdomains in HEK cells. Our results indicate that Kv1.5 partnership interactions are underlying mechanisms governing channel targeting to lipid rafts.
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影响因子：
3.5
作者：
Pannasch, Ulrike;Faerber, Katrin;Kettenmann, Helmut
通讯作者：
Kettenmann, Helmut
影响因子：
4.5
作者：
Hajdú, P;Varga, Z;Gaspar, R
通讯作者：
Gaspar, R
影响因子：
4.8
作者：
Martens, JR;Navarro-Polanco, R;Tamkun, MM
通讯作者：
Tamkun, MM
影响因子：
9.2
作者：
Nichols, BJ
通讯作者：
Nichols, BJ
影响因子：
3.5
作者：
Eldstrom, Jodene;Van Wagoner, David R.;Fedida, David
通讯作者：
Fedida, David