科大蛋白研究或可破解男性不育难题

　　

生物通报道，来自香港科技大学生物化学系，生物系，以及香港中文大学健康科学研究所的科研人员在最新一期的The Journal of Clinical Investigation上发表关于男性不育的最新研究进展。

 

文章通讯作者是香港科技大学的副教授夏军，2001于Johns Hopkins获得博士学位，主要从事神经突触转导研究，以及学习与记忆的分子机制研究。

 

Globozoospermia（圆头精子症，又名round-headed spermatozoa）是一种以精子顶体异常为主要特征的不育综合症，是一种罕见的不育疾病。夏军教授以及其香港科技大学的同事在一项新的研究中以雄性小鼠为研究模型，找出一种与不育有关的蛋白，PICK1，深入研究发现缺乏PICK1的雄性小鼠其临床上的表征与人类男性圆头精子症类似，这一结果可能对研究人类男性圆头精子症有借鉴意义。

 

在小鼠模型中，缺乏PICK1蛋白会导致精子计数低，并且有限的精子异型（圆头），导致精子的游动能力受到极大的破坏。对这些异常的精子进行深入研究发现，精子的顶体发生畸变，正常来说顶体中含有特殊的蛋白能帮助精子穿透卵子的外层达到受精的作用。研究发现PICK1与顶体细胞结构中的另外两种蛋白有密切的联系，分别是GOPC和CK2-alpha。

 

这些结果表明，PICK1蛋白是促进精子顶体发育的关键蛋白，缺失PICK1蛋白将导致精子受破坏，失去活动能力和受精能力。这一研究成果可能对男性不育的治疗有新的意。

（生物通 小茜）

 

生物通推荐原文：TITLE: PICK1 deficiency causes male infertility in mice by disrupting acrosome formation

【Abstract】

Protein interacting with C kinase 1 (PICK1) is a peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. Here, we report that male mice deficient in PICK1 are infertile and have a phenotype resembling the human disease globozoospermia. The primary defect in the testes of Pick1-knockout mice was fragmentation of acrosomes in the early stages of spermiogenesis. This fragmentation was followed by defects in nuclear elongation and mitochondrial sheath formation, leading to round-headed sperm, reduced sperm count, and severely impaired sperm motility. We found that PICK1 interacted with Golgi-associated PDZ- and coiled-coil motif–containing protein (GOPC) and the primary catalytic subunit of protein kinase 2 (CK2α′), proteins whose deficiencies lead to globozoospermia in mice. PICK1 was highly expressed in round spermatids and localized to Golgi-derived proacrosomal granules. GOPC colocalized with PICK1 in the Golgi region and facilitated formation of PICK1-positive clusters. Furthermore, there was an increase in apoptosis in the seminiferous tubules of Pick1–/– mice, a phenotype also seen in CK2α′-deficient mice. Our results suggest that PICK1 is involved in vesicle trafficking from the Golgi apparatus to the acrosome and cooperates with other proteins such as GOPC and CK2α′ in acrosome biogenesis.

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