Assembly with the Na,K-ATPase α 1 Subunit Is Required for Export of β 1 and β 2 Subunits from the Endoplasmic Reticulum
Assembly with the Na,K-ATPase α 1 Subunit Is Required for Export of β 1 and β 2 Subunits from the Endoplasmic Reticulum
复制标题
DOI：
--
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
E. Tokhtaeva;G. Sachs;O. Vagin
中科院分区：
文献类型：
--
作者：
E. Tokhtaeva;G. Sachs;O. Vagin
异二聚体Na，K-ATP酶的水平在上皮中受到严格控制，以维持适当的转运功能。具有催化作用的Na，K-ATP酶α亚基不能离开内质网或催化离子转运，除非与β亚基组装在一起。然而，Na，K-ATP酶β亚基在细胞间粘附中起着额外的、不依赖于离子转运的作用，其对内质网出口的要求尚不清楚。在肾MDCK细胞中表达的外源性β 1或β 2亚基取代ER中α - β复合物中的内源性β 1亚基，导致α 1结合的内源性β 1亚基的量减少47-61%，而α 1亚基的量没有变化。通过β 1或β 2亚基的确定α 1相互作用区域中的突变破坏α 1 - β缔合，导致ER保留和未组装突变体的快速降解。因此，ER质量控制系统仅允许组装的α - β复合物输出到高尔基体，从而维持质膜中α和β亚基的等摩尔比，而ER中α 1亚基的数量决定α - β复合物的量。
The level of the heterodimeric Na,K-ATPase is tightly controlled in epithelia to maintain appropriate transport function. The catalytic Na,K-ATPase α subunit is not able to exit the ER or catalyze ion transport unless assembled with the β subunit. However, requirements for the ER exit of the Na,K-ATPase β subunit that plays an additional, ion-transport-independent, role in intercellular adhesion are not clear. Exogenous β 1 or β 2 subunits expressed in renal MDCK cells replace endogenous β 1 subunits in the α – β complexes in the ER, resulting in a decrease in the amount of the α 1 -bound endogenous β 1 subunits by 47–61% with no change in the amount of α 1 subunits. Disruption of the α 1 – β association by mutations in defined α 1 -interacting regions of either β 1 or β 2 subunits results in the ER retention and rapid degradation of unassembled mutants. Hence, the ER quality control system allows export only of assembled α – β complexes to the Golgi, thereby maintaining an equimolar ratio of α and β subunits in the plasma membrane, whereas the number of α 1 subunits in the ER determines the amount of the α – β complexes.