Trafficking and surface expression of the glutamate receptor subunit, KA2
Trafficking and surface expression of the glutamate receptor subunit, KA2
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DOI：
10.1016/j.bbrc.2003.08.115
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发表时间：
2003-10-10
影响因子：
3.1
通讯作者：
Roche, KW
中科院分区：
文献类型：
--
作者：
Hayes, DM;Braud, S;Roche, KW
盐酸盐受体是一类在哺乳动物大脑中广泛表达的嗜离子型谷氨酸受体，但对其生理作用和调控机制知之甚少。盐酸盐受体由多个亚基（GluR5-7; KA1-2）组成，这些亚基可以结合形成同质或异质通道。盐酸盐受体亚基KA2可以与GluR5-7结合形成异质通道，但单独表达时不能形成功能性同质通道。为了确定其分子机制，我们对KA2的转运和表面表达进行了表征。我们发现KA2单独不运输到质膜，并保留在内质网（ER）。相反，与GluR6的共表达破坏了KA2的er保留，并允许质膜表达。利用嵌合报告蛋白，我们在KA2细胞质结构域中鉴定了er保留基序。最近的研究已经确定了一个共识的ER-retention motif (RRR)，它包含在NMDA受体NR1亚基和K+通道中。虽然KA2在其c端（RRRRR）中含有类似的氨基酸延伸，但与NR1基序不同，用交替的谷氨酸残基破坏该基序不会破坏KA2的er保留，这表明调节KA2表面表达的独特机制。Elsevier Inc.出版。
Kainate receptors are a class of ionotropic glutamate receptors that are widely expressed in the mammalian brain, yet little is known about their physiological role or the mechanisms by which they are regulated. Kainate receptors are composed of multiple subunits (GluR5-7; KA1-2), which can combine to form homomeric or heteromeric channels. While the kainate receptor subunit KA2 can combine with GluR5-7 to form heteromeric channels, it does not form functional homomeric channels when expressed alone. In an attempt to identify the molecular mechanisms for this, we have characterized the trafficking and surface expression of KA2. We find that KA2 alone does not traffic to the plasma membrane and is retained in the endoplasmic reticulum (ER). In contrast, co-expression with GluR6 disrupts ER-retention of KA2 and allows plasma membrane expression. Using a chimeric reporter protein we have identified an ER-retention motif within the KA2 cytosolic domain. Recent studies have identified a consensus ER-retention motif (RRR) that is contained within both the NMDA receptor NR1 subunit and K+ channels. While KA2 contains a similar stretch of amino acids within its C-terminus (RRRRR), unlike the NR1 motif, disruption of this motif with alternating glutamic acid residues does not disrupt ER-retention of KA2, suggesting a unique mechanism regulating KA2 surface expression. Published by Elsevier Inc.