SEPT12-microtubule complexes are required for sperm head and tail formation.
SEPT12-microtubule complexes are required for sperm head and tail formation.
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DOI：
10.3390/ijms141122102
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发表时间：
2013-11-07
影响因子：
5.6
通讯作者：
Lin YH
中科院分区：
文献类型：
--
作者：
Kuo PL;Chiang HS;Wang YY;Kuo YC;Chen MF;Yu IS;Teng YN;Lin SW;Lin YH
Septin基因属于高度保守的GTP结合细胞骨架蛋白聚合家族。SEPT通过与不同的细胞骨架相互作用，执行细胞骨架重塑、细胞极性、有丝分裂和囊泡运输。我们以前的研究表明，带有SEPTIN12突变等位基因的SEPTIN12+/−嵌合体是不育的。来自嵌合小鼠输精管的精子显示精子形态异常，精子数量减少，精子不能活动。不育患者中SEPTIN12的突变和基因变异也会导致少精子症和畸精症。我们认为SEPT12的缺失影响微管蛋白功能的生物学功能，并导致精子发生缺陷。在细胞模型中，SEPT12通过免疫共沉淀(co-IP)与α-和β-微管蛋白相互作用。为了确定SEPT12和α-和β-微管蛋白在体内的精确定位和相互作用，我们建立了SEPTIN12转基因小鼠。我们展示了SEPT12如何在这些小鼠的精子发生过程中与α-和β-微管蛋白相互作用和共同定位。通过使用shRNA，SEPT12转录本的丢失破坏了α-和β-微管蛋白的组织。此外，在SEPTIN12+/α嵌合体中，SEPT12的丢失或减少干扰了精子头部的形态发生和精子尾部的伸长，其步骤由β-微管蛋白和−-微管蛋白协调和构建。在这项研究中，我们发现SEPTIN12-微管复合体在精子发生过程中对精子的形成至关重要。
The septin gene belongs to a highly conserved family of polymerizing GTP-binding cytoskeletal proteins. SEPTs perform cytoskeletal remodeling, cell polarity, mitosis, and vesicle trafficking by interacting with various cytoskeletons. Our previous studies have indicated that SEPTIN12+/+/+/− chimeras with a SEPTIN12 mutant allele were infertile. Spermatozoa from the vas deferens of chimeric mice indicated an abnormal sperm morphology, decreased sperm count, and immotile sperm. Mutations and genetic variants of SEPTIN12 in infertility cases also caused oligozoospermia and teratozoospermia. We suggest that a loss of SEPT12 affects the biological function of microtublin functions and causes spermiogenesis defects. In the cell model, SEPT12 interacts with α- and β-tubulins by co-immunoprecipitation (co-IP). To determine the precise localization and interactions between SEPT12 and α- and β-tubulins in vivo, we created SEPTIN12-transgene mice. We demonstrate how SEPT12 interacts and co-localizes with α- and β-tubulins during spermiogenesis in these mice. By using shRNA, the loss of SEPT12 transcripts disrupts α- and β-tubulin organization. In addition, losing or decreasing SEPT12 disturbs the morphogenesis of sperm heads and the elongation of sperm tails, the steps of which are coordinated and constructed by α- and β-tubulins, in SEPTIN12+/+/+/− chimeras. In this study, we discovered that the SEPTIN12-microtubule complexes are critical for sperm formation during spermiogenesis.
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影响因子：
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