RRC ID 5334
Author Lin YN, Roy A, Yan W, Burns KH, Matzuk MM.
Title Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis.
Journal Mol. Cell. Biol.
Abstract Zona pellucida binding protein 1 (ZPBP1), a spermatid and spermatozoon protein that localizes to the acrosome, was originally identified in pigs and named for its binding to the oocyte zona pellucida. In an in silico search for germ cell-specific genes, Zpbp1 and its novel paralog, Zpbp2, were discovered and confirmed to be expressed only in the testes in both mice and humans. To study the in vivo functions of both ZPBP proteins, we disrupted Zpbp1 and Zpbp2 in mice. Males lacking ZPBP1 were sterile, with abnormal round-headed sperm morphology and no forward sperm motility. Ultrastructural studies demonstrated that absence of ZPBP1 prevents proper acrosome compaction, resulting in acrosome fragmentation and disruption of the Sertoli-spermatid junctions. Males null for ZPBP2 were subfertile, demonstrated aberrant acrosomal membrane invaginations, and produced dysmorphic sperm with reduced ability to penetrate zona pellucida. Molecular phylogenetic analysis of ZPBPs from amphibians, birds, and mammals suggests that these paralogous genes coevolved to play cooperative roles during spermiogenesis. Whereas ZPBP1 was discovered for an in vitro role in sperm-egg interactions, we have shown that both ZPBP proteins play an earlier structural role during spermiogenesis.
Volume 27(19)
Pages 6794-805
Published 2007-10
DOI 10.1128/MCB.01029-07
PII MCB.01029-07
PMID 17664285
PMC PMC2099232
MeSH Acrosome / metabolism* Acrosome / ultrastructure Amino Acid Sequence Animals Egg Proteins / genetics Egg Proteins / metabolism* Fertilization Humans Infertility, Male Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Knockout Molecular Sequence Data Morphogenesis* Multigene Family Protein Isoforms / genetics Protein Isoforms / metabolism Protein Processing, Post-Translational Sequence Alignment Sequence Homology, Amino Acid Spermatozoa* / abnormalities Spermatozoa* / metabolism Spermatozoa* / ultrastructure Swine Zona Pellucida / metabolism
IF 3.735
Times Cited 83