研究人員最近發(fā)現(xiàn)一個(gè)卵子受精相關(guān)蛋白,，為發(fā)展生殖技術(shù)和治療生殖系統(tǒng)疾病提供了重要信息。
精子頭部細(xì)胞膜與卵子細(xì)胞膜開始融合時(shí),，兩個(gè)細(xì)胞之間出現(xiàn)一個(gè)“開口”,，精子釋放蛋白激活卵子，精子由此進(jìn)一步進(jìn)入卵子,，精卵融合形成受精卵,。盡管激活卵子的步驟已經(jīng)被研究的很清楚，但具體啟動(dòng)活化過程的分子還不為人知,。
Richard Oko與其同事發(fā)現(xiàn)一種在激活卵子的第一個(gè)階段發(fā)揮關(guān)鍵作用的新蛋白,。這種蛋白在許多物種中都存在，Oko等將其命名為后頂體鞘WW區(qū)-結(jié)合蛋白（postacrosomal sheath WW domain-binding protein,，PAWP）,。研究人員阻斷功能性精子的PAWP，然后通過一種常見的體外受精技術(shù)——卵細(xì)胞質(zhì)內(nèi)單精子注射技術(shù)（Intracytoplasmic sperm injection,，ICSI）將精子注射到卵子中,，結(jié)果缺少了PAWP的精子不能激活卵子，證實(shí)該蛋白在啟動(dòng)活化過程中的作用,。研究人員還發(fā)現(xiàn)PAWP蛋白位于精子頭部區(qū)域,。
原始出處:
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. Wu1, 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.
