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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel
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LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel

机译：LRRC52（富含亮氨酸的重复蛋白52），是经碱化激活的Slo3通道的睾丸特异性辅助亚基

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摘要

KSper, a pH-dependent K~+ current in mouse spermatozoa that is critical for fertility, is activated by alkalization in the range of pH 6.4-7.2 at membrane potentials between -50 and 0 mV. Although the KSper pore-forming subunit is encoded by the Slo3 gene, heterologously expressed Slo3 channels are largely closed at potentials negative to 0 mV at physiological pH. Here we identify a Slo3-associating protein, LRRC52 (leucine-rich repeat-containing 52), that shifts Slo3 gating into a range of voltages and pH values similar to that producing KSper current activation. Message for LRRC52, a homolog of the Slo1-modifying LRRC26 protein, is enriched in testis relative to other homologous LRRC subunits and is developmentally regulated in concert with that for Slo3. LRRC52 protein is detected only in testis. It is markedly diminished from Slo3~(-/-) testis and completely absent from Slo3~(-/-) sperm, indicating that LRRC52 expression is critically dependent on the presence of Slo3. We also examined the ability of other LRRC sub-units homologous to LRRC26 and LRRC52 to modify Slo3 currents. Although both LRRC26 and LRRC52 are able to modify Slo3 function, LRRC52 is the stronger modifier of Slo3 function. Effects of other related subunits were, weaker or absent. We propose that LRRC52 is a testis-enriched Slo3 auxiliary subunit that helps define the specific alkalization dependence of KSper activation. Together, LRRC52 and LRRC26 define a new family of auxiliary subunits capable of critically modifying the gating behavior of Slo family channels.
机译：KSper是小鼠精子中pH依赖性的K〜+电流，对生育能力至关重要。KSper是在pH值为6.4-7.2的范围内在-50至0 mV的膜电位下被碱化激活的。尽管KSper孔形成亚基由Slo3基因编码，但在生理pH值下，异源表达的Slo3通道在负电势为0 mV的情况下很大程度上关闭。在这里，我们确定了一个Slo3相关蛋白LRRC52（富含亮氨酸的重复序列52），它将Slo3门控转变为类似于产生KSper电流激活的电压和pH值范围。 LRRC52（修饰Slo1的LRRC26蛋白的同系物）的信息相对于其他同源LRRC亚基在睾丸中富集，并且与Slo3的信息共同受到发育调控。 LRRC52蛋白仅在睾丸中检测到。 Slo3〜（-/-）精子明显减少，而Slo3〜（-/-）精子完全不存在，表明LRRC52的表达主要取决于Slo3的存在。我们还检查了与LRRC26和LRRC52同源的其他LRRC子单元修饰Slo3电流的能力。尽管LRRC26和LRRC52都可以修改Slo3功能，但LRRC52是Slo3功能的更强大的修改器。其他相关亚基的作用较弱或不存在。我们建议LRRC52是一个丰富的睾丸Slo3辅助亚基，有助于定义KSper活化的特定碱化依赖性。 LRRC52和LRRC26共同定义了一个新的辅助亚基家族，它们能够严格修饰Slo家族通道的门控行为。

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    Chengtao Yang; Xu-Hui Zeng; Yu Zhou; Xiao-Ming Xia; Christopher J. Lingle;

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    Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110;

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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