A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility

Nobuyoshi Takasaki, Kouichi Tachibana, Satoshi Ogasawara, Hideki Matsuzaki, Jun Hagiuda, Hiromichi Ishikawa, Keiji Mochida, Kimiko Inoue, Narumi Ogonuki, Atsuo Ogura, Toshiaki Noce, Chizuru Ito, Kiyotaka Toshimori, Hisashi Narimatsu

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1120-1125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
Publication statusPublished - 2014 Jan 21

ASJC Scopus subject areas

  • General


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