title: Complementary role of CNNM2 in sperm motility and Ca(2+) influx during capacitation.
abstract: Ca(2+) plays a central role in the regulation of sperm motility. We recently reported an unexpected role of CNNM4, a Mg(2+) transporter, in this process by demonstrating perturbed Ca(2+) influx and gradual loss of motility of Cnnm4-deficient sperm. However, Cnnm4-deficient male mice were not entirely infertile, and a significant Ca(2+) response was still observed in their sperm. In the present study, we generated Cnnm4-deficient mice harboring a non-functional Cnnm2 allele (Cnnm2(Δ)), to examine whether CNNM2 compensates for the lost function of CNNM4 in sperm. Cnnm2(+/Δ); Cnnm4(Δ/Δ) mice were infertile, and no obvious histological abnormalities were noted in their testis and epididymis. Their sperm showed normal morphology, but became immotile much more rapidly than those from Cnnm4(Δ/Δ) mice. When capacitation was initiated using serum albumin application, a rapid increase of intracellular Ca(2+) levels was observed in most wild-type sperm, but only about half of sperm from Cnnm4(Δ/Δ) mice exhibited a Ca(2+) response, and the response rate was further reduced in sperm from Cnnm2(+/Δ); Cnnm4(Δ/Δ) mice. Thus, sperm motility and Ca(2+) response were more severely affected in sperm from Cnnm2(+/Δ); Cnnm4(Δ/Δ) mice than in those from Cnnm4(Δ/Δ) mice, implicating CNNM2 in regulating these processes.
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamazaki
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Funato
authors.affiliation: Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: hmiki@biken.osaka-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D027682:Cation Transport Proteins / Q000378:metabolism*; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D013075:Sperm Capacitation; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C510868:Cnnm2 protein, mouse; D002118:Calcium
keywords: CNNM2; Ca(2+) influx; CatSper channel; Male fertility; Sperm motility