严伟实验室发表最新PNAS文章：新精子成熟基因

　　

生物通报道：在4月10日的PNAS网络版上发布了一篇由内华达州立大学医学院和夏威夷大学John. A. Burns医学院的研究人员的研究报告。他们发现了一种新的精子成熟基因Spem1，缺失这种基因会导致细胞质的异常移动、精子变形和雄性不育。

这项研究领导者之一是华人学者严伟（Wei Yan）助理教授，文章的第一作者是严伟实验室的郑慧丽（Huili Zheng）博士。

这个研究组确定出了一种新的基因Spem1（精子成熟基因）。在小鼠睾丸中，该基因编码一种只在14到16步骤的拉伸精细胞的细胞质中表达。

这种蛋白质没有人们已知的功能结构域，并且在哺乳动物种类间高度保守。雄性小鼠如果缺少Spem1基因，就会因为精子变形而彻底不育。

这项研究显示，缺少Spem1基因会导致细胞质变得松散，并且从发育中的精子细胞的头、颈区域分离。滞留的细胞质成分则会阻塞精子头部的垂直和尾部的拉伸，从而导致头部弯曲在颈部，进而颈部或精子尾巴的中间部分包裹住精子头部。

这项新研究揭示出，适当的细胞质移动在基因水平的调节过程需要Spem1基因的参与，并且缺失Spem1基因会导致精子变形和雄性不育。（生物通杨遥）

附：严伟研究组研究方向介绍及发表论文精选

 

Regulation of Mammalian Gametogenesis

We are interested in how gametes, sperm and oocytes, are produced in mammals. In particular, we investigate which of the germ cell-specific genes are essential for successful production of gametes and which particular molecular pathways they are involved in. We utilize gene knockout technologies and molecular biology approaches to define physiological roles of these genes and the molecular mechanisms by which they regulate germ cell development. Currently, our efforts are focused on the following three topics: (1) the regulation of protein turnover by ubiquitination during spermiogenesis; (2) the control of cytoplasm removal during sperm individualization and spermiation (sperm release); (3) physiological roles of germ cell-specific small non-coding RNAs. Our study is important not only for the identification of causative genes of human infertility, but also for the development of non-hormonal contraceptives.

The Yan Lab Members:

Jingling Jin, PhD, Post-doc
Chanjae Park, PhD, Post-doc
Steven Rui Song, BSc, Graduate Student
Shouhua Wang, PhD, Graduate Student
Yan Guo, MD, Graduate Student
David Young, Undergraduate Student
Dora Tafolla, BSc, Technician
Huili Zheng, MD, PhD, Senior Research Associate, Lab Manager

论文精选：

Yan W, Suominen J, Toppari J (2000) Stem cell factor protects germ cells from apoptosis in vitro. Journal of Cell Science 113:161-168

Yan W, Kero J, Huhtaniemi I, Toppari J (2000) Stem cell factor functions as a survival factor for mature Leydig cells and a growth factor for precursor Leydig cells after ethylene dimethane sulfonate treatment: implication of the role of stem cell factor/c-kit interaction in Leydig cell development. Developmental Biology 227:169-182

Yan W, Kero J, Suominen J, Toppari J (2001) Differential expression and regulation of retinoblastoma protein (pRb) family members during testicular development and spermatogenesis: a model for the control of germ cell proliferation, differentiation and apoptosis in vivo. Oncogene 20: 1343–1356

Yan W, Assadi AH, Wynshaw-Boris A, Eichele G, Matzuk MM, Clark GD (2003) A novel role for platelet-activating factor acetylhydrolase 1b in mouse spermatogenesis. Proceedings of the National Academy of Sciences USA 100:7189-7194.

Yan W, Huang JX, Lax AS, Pelliniemi L, Salminen E, Poutanen M, Toppari J (2003) Overexpression of Bcl-w in the testis disrupts spermatogenesis: revelation of a role of BCL-W in male germ cell cycle control. Molecular Endocrinology 17:1868-1879.

Yan W, Ma L, Burns KH, Matzuk MM (2003) Identification of a novel spermatid-specific linker histone H1 involved in chromatin remodeling during mammalian spermiogenesis. Proceedings of the National Academy of Sciences USA 100:10546-10551.

Yan W, Ma L, Matzuk MM (2004) Haploinsufficiency of KLHL10 causes male infertility. Proceedings of the National Academy of Sciences USA 101:7793-7798.

Yan W, Ma L, Stein P, Pangas SA, Burns KH, Bai, YC, Schultz, RM,, Matzuk, MM (2005) Mice deficient in oocyte-specific oligoadenylate synthetase-like protein OAS1D display reduced fertility. Molecular and Cellular Biology 25:4615-4624.

Jin JL, O’Doherty AM, Wang SH, Zheng HL, Sanders KM, Yan W (2005) Catsper3 and Catsper4 encode two cation channel-like proteins exclusively expressed in the testis. Biology of Reproduction 73:1235-1242

Greenbaum MP, Yan W*, Wu MH, Lin YN, Agno JE, Sharma M, Braun RE, Rajkovic A, Matzuk MM. (2006) TEX14 is essential for intercellular bridges and fertility in male mice. Proceedings of the National Academy of Sciences USA 103(13):4982-7. (*co-first authors)

Wang SH, Zheng HL, Esaki Y, Kelly F, Yan W (2006) Cullin3 is a KLHL10-interacting protein preferentially expressed during late spermiogenesis. Biology of Reproduction 74:102-108

Ro S, Park C, Jin J, Sanders KM, Yan W (2006) A PCR-based method for detection and quantification of small RNAs. Biochemical and Biophysical Research Communications 351:756-763.

Zheng H, Stratton CJ, Morozumi K, Jin J, Yanagimachi R, Yan W (2007) Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation and male infertility. Proceedings of the National Academy of Sciences USA In Press

Jin J, Jin N, Zheng H, Ro S, Tafolla D, Sanders KM, Yan W (2007) Catsper3 and Catsper4 are Essential for Sperm Hyperactivated Motility and Male Fertility. Biology of Reproduction In Press

 想了解更多该实验室信息可登陆以下网址：http://www.unr.edu/physio/facyan.html

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