PAWP, a sperm-specific WW domain-binding protein, promotes meiotic resumption and pronuclear development during fertilization

Alexander T H Wu, Peter Sutovsky, Gaurishankar Manandhar, Wei Xu, Mika Katayama, Billy N. Day, Kwang Wook Park, Young Joo Yi, Wei Xi Yan, Randall S. Prather, Richard Oko

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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 IWW 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.

Original languageEnglish
Pages (from-to)12164-12175
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number16
DOIs
Publication statusPublished - Apr 20 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Wu, A. T. H., Sutovsky, P., Manandhar, G., Xu, W., Katayama, M., Day, B. N., Park, K. W., Yi, Y. J., Yan, W. X., Prather, R. S., & Oko, R. (2007). PAWP, a sperm-specific WW domain-binding protein, promotes meiotic resumption and pronuclear development during fertilization. Journal of Biological Chemistry, 282(16), 12164-12175. https://doi.org/10.1074/jbc.M609132200