The putative chaperone calmegin is required for sperm fertility.
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 proteins. In contrast to other known chaperones such as heat-shock proteins, BiP and calreticulin, calnexin is an integral membrane protein. Calmegin is a testis-specific ER protein that is homologous to calnexin. 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.
Ikawa
M
M
Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Wada
I
I
Kominami
K
K
Watanabe
D
D
Toshimori
K
K
Nishimune
Y
Y
Okabe
M
M
D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D037281:Calnexin; D018833:Chaperonins / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D005306:Fertilization; D018390:Gene Targeting; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D013084:Sperm-Ovum Interactions / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology*; D015044:Zona Pellucida / Q000502:physiology
D002135:Calcium-Binding Proteins; D018832:Molecular Chaperones; D037281:Calnexin; C087341:calmegin; D018833:Chaperonins