Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers
Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers
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DOI：
10.1242/jcs.02322
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发表时间：
2005-05-01
影响因子：
4
通讯作者：
Klöcker, N
中科院分区：
文献类型：
--
作者：
Hofherr, A;Fakler, B;Klöcker, N
离子通道和受体的表面表达通常依赖于内在序列基序，该基序控制它们沿分泌途径的细胞内转运沿着。虽然Kir2.x亚家族的成员共有两个这样的基序-一个二酸ER输出基序和一个带正电荷的高尔基体输出基序-但它们在表面表达上存在很大差异。而Kir2.1显示出突出的质膜定位，Kir2.4通道聚集在高尔基复合体内。通过构建Kir2.1和Kir2.4亚基之间的嵌合体，在Kir2.1 C-末端鉴定了一段20个氨基酸，这对于在从高尔基体到质膜的运输水平上促进Kir通道亚基的顺行运输是必要的和足够的。所鉴定序列的核心元件具有用于衔接蛋白结合的酪氨酸依赖性YXX Phi共有基序，侧翼残基决定其功能效率。由于该信号在促进Kir2.1/Kir2.4通道异聚体的表面转运中占主导地位，并且被上皮细胞和神经元细胞内分选机制识别，因此Kir2.1的优先高尔基体输出将控制在细胞表面上表达的Kir2.x异聚体的化学计量。
Surface expression of ion channels and receptors often depends on intrinsic sequence motifs that control their intracellular transport along the secretory pathway. Although members of the Kir2.x subfamily share two such motifs - a diacidic ER export motif and a positively charged Golgi export motif - they strongly differ in their surface expression. Whereas Kir2.1 shows prominent plasma membrane localization, Kir2.4 channels accumulate within the Golgi complex. By constructing chimeras between Kir2.1 and Kir2.4 subunits, a stretch of 20 amino acids was identified in the Kir2.1 C-terminus that is both necessary and sufficient to promote anterograde transport of Kir channel subunits at the level of trafficking from the Golgi to the plasma membrane. The core element of the identified sequence bears a tyrosine-dependent YXX Phi consensus motif for adaptin binding, with the flanking residues determining its functional efficiency. As the signal is dominant in promoting surface transport of Kir2.1/Kir2.4 channel heteromers and is recognized by both the epithelial and neuronal intracellular sorting machinery, the preferential Golgi export of Kir2.1 will control the stoichiometry of Kir2.x heteromers expressed on the cell surface.