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细胞质中的 Slo3 同工型在体组织中表达。

A cytoplasmic Slo3 isoform is expressed in somatic tissues.

机构信息

Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Austónoma de México, Avenida Universidad 2001, Col. Chamilpa, 62210, Cuernavaca, Morelos, Mexico.

Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310, Vigo, Spain.

出版信息

Mol Biol Rep. 2019 Oct;46(5):5561-5567. doi: 10.1007/s11033-019-04943-z. Epub 2019 Jul 3.

Abstract

Slo3 is a pH-sensitive and weakly voltage-sensitive potassium channel that is essential for male fertility in mouse and whose expression is regarded as sperm-specific. These properties have proposed Slo3 as a candidate target for male contraceptive drugs. Nonetheless, the tissue distribution of Slo3 expression has not been rigorously studied yet. Applying computational and RT-PCR approaches, we identified expression of two short Slo3 isoforms in somatic mouse tissues such as brain, kidney and eye. These isoforms, which seem to result of transcription starting sites between exons 20 and 21, have an identical open reading frame, both encoding the terminal 381 amino acids of the cytosolic Slo3 domain. We corroborated the expression of these isoforms in mouse brain and testis by Western-blot. The complete isoform encoding the Slo3 ion channel was uniquely detected in testis, both at transcript and protein level. Although the functional role of the cytosolic Slo3 isoforms remains to be established, we propose that they may have a functional effect by modulating Slo channels trafficking and/or activity. This study confirms that expression of full-length Slo3 is sperm-specific but warns against developing contraceptive drugs targeting the C-terminal tail of Slo3 channels.

摘要

Slo3 是一种 pH 敏感且电压敏感性较弱的钾通道,对于小鼠的雄性生育力至关重要,其表达被认为是精子特异性的。这些特性使 Slo3 成为男性避孕药候选靶点。然而,Slo3 表达的组织分布尚未经过严格研究。通过计算和 RT-PCR 方法,我们在脑、肾和眼等体组织中鉴定出两种短 Slo3 亚型的表达。这些亚型似乎是由外显子 20 和 21 之间的转录起始位点产生的,具有相同的开放阅读框,均编码细胞质 Slo3 结构域的末端 381 个氨基酸。我们通过 Western blot 证实了这些亚型在小鼠脑和睾丸中的表达。编码 Slo3 离子通道的完整亚型仅在睾丸中以转录本和蛋白质水平检测到。尽管细胞质 Slo3 亚型的功能作用仍有待确定,但我们提出它们可能通过调节 Slo 通道运输和/或活性产生功能效应。本研究证实全长 Slo3 的表达是精子特异性的,但警告不要开发针对 Slo3 通道 C 末端的避孕药物。

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