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首页> 外文期刊>Molecular and Cellular Biology >Direct Interaction with Rab11a Targets the Epithelial Ca2+ Channels TRPV5 and TRPV6 to the Plasma Membrane
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Direct Interaction with Rab11a Targets the Epithelial Ca2+ Channels TRPV5 and TRPV6 to the Plasma Membrane

机译:与Rab11a的直接相互作用靶向上皮Ca2 +通道TRPV5和TRPV6到达质膜。

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TRPV5 and TRPV6 are the most Ca2+-selective members of the transient receptor potential (TRP) family of cation channels and play a pivotal role in the maintenance of Ca2+ balance in the body. However, little is known about the mechanisms controlling the plasma membrane abundance of these channels to regulate epithelial Ca2+ transport. In this study, we demonstrated the direct and specific interaction of GDP-bound Rab11a with TRPV5 and TRPV6. Rab11a colocalized with TRPV5 and TRPV6 in vesicular structures underlying the apical plasma membrane of Ca2+-transporting epithelial cells. This GTPase recognized a conserved stretch in the carboxyl terminus of TRPV5 that is essential for channel trafficking. Furthermore, coexpression of GDP-locked Rab11a with TRPV5 or TRPV6 resulted in significantly decreased Ca2+ uptake, caused by diminished channel cell surface expression. Together, our data demonstrated the important role of Rab11a in the trafficking of TRPV5 and TRPV6. Rab11a exerts this function in a novel fashion, since it operates via direct cargo interaction while in the GDP-bound configuration.
机译:TRPV5和TRPV6是阳离子通道瞬态受体电位(TRP)家族中对Ca 2 + 选择性最高的成员,在维持Ca 2 + 方面起着关键作用身体平衡。然而,关于控制这些通道质膜丰度以调节上皮Ca 2 + 转运的机制知之甚少。在这项研究中,我们证明了GDP绑定的Rab11a与TRPV5和TRPV6的直接和特定的相互作用。 Rab11a与TRPV5和TRPV6在Ca 2 + 转运上皮细胞顶质膜下的囊泡结构中共定位。该GTP酶在TRPV5的羧基末端识别了保守的延伸,这对于通道运输至关重要。此外,GDP锁定的Rab11a与TRPV5或TRPV6的共表达导致通道细胞表面表达减少,导致Ca 2 + 吸收显着降低。我们的数据在一起证明了Rab11a在TRPV5和TRPV6的贩运中的重要作用。 Rab11a以新颖的方式发挥了这一功能,因为它在GDP限制的状态下通过直接的货物相互作用进行操作。

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