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The putative chaperone calmegin is required for sperm fertility

Nature volume 387, pages 607–611 (1997)Cite this article

Abstract

The proper folding of newly synthesized membrane proteins in the endoplasmic reticulum (ER) is required for the formation of functional mature proteins. Calnexin is a ubiquitous ER chaperone that plays a major role in quality control by retaining incompletely folded or misfolded proteins1,2,3,4,5. In contrast to other known chaperones such as heat-shock proteins, BiP and calreticulin, calnexin is an integral membrane protein1,6. Calmegin is a testis-specific ER protein that is homologous to calnexin7,8,9. Here we show that calmegin binds to nascent polypeptides during spermatogenesis, and have analysed its physiological function by targeted disruption of its gene. Homozygous-null male mice are nearly sterile even though spermatogenesis is morphologically normal and mating is normal. In vitro, sperm from homozygous-null males do not adhere to the egg extracellular matrix (zona pellucida), and this defect may explain the observed infertility. These results suggest that calmegin functions as a chaperone for one or more sperm surface proteins that mediate the interactions between sperm and egg. The defective zona pellucida-adhesion phenotype of sperm from calmegin-deficient mice is reminiscent of certain cases of unexplained infertility in human males.

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Figure 1: Calmegin and calnexin interact with nascent glycoproteins during spermatogenesis.
Figure 2: Targeted disruption of calmegin gene.
Figure 3: Sperm from calmegin-deficient and wild-type mice were stained with anti-acrosomal monoclonal and polyclonal antibodies (OBF13, MC101, MN17, MN9, sp56 and PH-20; see Methods).
Figure 4: Sperm from +/+ mice successfully adhered to the eggs (a), but those from −/− mice failed to attach despite frquent collisions with the zona pellucida (b).

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Acknowledgements

We thank P. Primakoff for the anti-PH-20 antibody and B. Storey, G. Gerton and D.Hardy for comments.

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Authors and Affiliations

  1. Research Institute for Microbial Diseases, Osaka University, 3-1 Suita, 565, Osaka, Japan

    Masahito Ikawa, Katsuya Kominami, Daisuke Watanabe, Yoshitake Nishimune & Masaru Okabe

  2. *Department of Biochemistry, Sapporo Medical University School of Medicine, 060, Sapporo, Japan

    Ikuo Wada

  3. †Department of Anatomy, Medical College of Miyazaki, 889-16, Miyazaki, Japan

    Kiyotaka Toshimori

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  1. Masahito Ikawa
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Correspondence to Masaru Okabe.

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Ikawa, M., Wada, I., Kominami, K. et al. The putative chaperone calmegin is required for sperm fertility. Nature 387, 607–611 (1997). https://doi.org/10.1038/42484

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