JBC：新发现一种精子用于激活卵子的蛋白
研究人员最近发现一个卵子受精相关蛋白，为发展生殖技术和治疗生殖系统疾病提供了重要信息。
精子头部细胞膜与卵子细胞膜开始融合时，两个细胞之间出现一个“开口”，精子释放蛋白激活卵子，精子由此进一步进入卵子，精卵融合形成受精卵。尽管激活卵子的步骤已经被研究的很清楚，但具体启动活化过程的分子还不为人知。
Richard Oko与其同事发现一种在激活卵子的第一个阶段发挥关键作用的新蛋白。这种蛋白在许多物种中都存在，Oko等将其命名为后顶体鞘WW区-结合蛋白（postacrosomal sheath WW domain-binding protein，PAWP）。研究人员阻断功能性精子的PAWP，然后通过一种常见的体外受精技术——卵细胞质内单精子注射技术（Intracytoplasmic sperm injection，ICSI）将精子注射到卵子中，结果缺少了PAWP的精子不能激活卵子，证实该蛋白在启动活化过程中的作用。研究人员还发现PAWP蛋白位于精子头部区域。
原始出处:
J. Biol. Chem., Vol. 282, Issue 16, 12164-12175, April 20, 2007
PAWP, a Sperm-specific WW Domain-binding Protein, Promotes Meiotic Resumption and Pronuclear Development during Fertilization*
Alexander T. H. Wu
1, Peter Sutovsky
¶1, Gaurishankar Manandhar, Wei Xu, Mika Katayama, Billy N. Day, Kwang-Wook Park, Young-Joo Yi, Yan Wei Xi||, Randall S. Prather, and Richard Oko2
From the Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada, the Departments of Animal Sciences and ¶Obstetrics and Gynecology, University of Missouri, Columbia, Missouri 65211-5300, and the ||Center for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, 20 Marie-Curie, Ottawa, Ontario K1N 6N5, Canada
We report a novel alkaline extractable protein of the sperm head that exclusively resides in the post-acrosomal sheath region of the perinuclear theca (PT) and is expressed and assembled in elongating spermatids. It is a protein that shares sequence homology to the N-terminal half of WW domain-binding protein 2, while the C-terminal half is unique and rich in proline. A functional PPXY consensus binding site for group-I WW domain-containing proteins, and numerous unique repeating motifs, YGXPPXG, are identified in the proline-rich region. Considering these molecular characteristics, we designated this protein PAWP for postacrosomal sheath WW domain-binding protein. Microinjection of recombinant PAWP or alkaline PT extract into metaphase II-arrested porcine, bovine, macaque, and Xenopus oocytes induced a high rate of pronuclear formation, which was prevented by co-injection of a competitive PPXY motif containing peptide derived from PAWP but not by co-injection of the point-mutated peptide. Intracytoplasmic sperm injection (ICSI) of porcine oocytes combined with co-injection of the competitive PPXY peptide or an anti-recombinant PAWP antiserum prevented pronuclear formation and arrested fertilization. Conversely, co-injection of the modified PPXY peptide, when the tyrosine residue of PPXY was either phosphorylated or substituted with phenylalanine, did not prevent ICSI-induced fertilization. This study uncovers a group I WW domain module signal transduction event within the fertilized egg that appears compulsory for meiotic resumption and pronuclear development during egg activation and provides compelling evidence that a PPXY motif of sperm-contributed PAWP can trigger these events.
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