title: A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility.
abstract: For normal fertilization in mammals, it is important that functionally mature sperm are motile and have a fully formed acrosome. The glycosyltransferase-like gene, human polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5), belongs to the polypeptide N-acetylgalactosamine-transferase (pp-GalNAc-T) gene family because of its conserved glycosyltransferase domains, but it uniquely truncates the C-terminal domain and is expressed exclusively in human testis. However, glycosyltransferase activity of the human GALNTL5 protein has not been identified by in vitro assay thus far. Using mouse Galntl5 ortholog, we have examined whether GALNTL5 is a functional molecule in spermatogenesis. It was observed that mouse GALNTL5 localizes in the cytoplasm of round spermatids in the region around the acrosome of elongating spermatids, and finally in the neck region of spermatozoa. We attempted to establish Galntl5-deficient mutant mice to investigate the role of Galntl5 in spermiogenesis and found that the heterozygous mutation affected male fertility due to immotile sperm, which is diagnosed as asthenozoospermia, an infertility syndrome in humans. Furthermore, the heterozygous mutation of Galntl5 attenuated glycolytic enzymes required for motility, disrupted protein loading into acrosomes, and caused aberrant localization of the ubiquitin-proteasome system. By comparing the protein compositions of sperm from infertile males, we found a deletion mutation of the exon of human GALNTL5 gene in a patient with asthenozoospermia. This strongly suggests that the genetic mutation of human GALNTL5 results in male infertility with the reduction of sperm motility and that GALNTL5 is a functional molecule essential for mammalian sperm formation.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Takasaki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tachibana
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Jun
authors.initials: J
authors.lastname: Hagiuda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Noce
authors.forename: Chizuru
authors.initials: C
authors.lastname: Ito
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Toshimori
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D000177:Acrosome / Q000378:metabolism; D000818:Animals; D053627:Asthenozoospermia / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D037102:Lectins / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D013081:Sperm Motility; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D037102:Lectins; D017350:N-Acetylgalactosaminyltransferases; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms; D025801:Ubiquitin; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C587353:GALNTL5 protein, human; C587354:GALNTL5 protein, mouse