CATSPER3 Membrane Protein Introduction

Introduction of CATSPER3

Catsper3 and Catsper4 are two recently identified testis-specific genes homologous to Catsper1 and Catsper2 that have been shown to play an essential role in sperm hyperactivated motility and male fertility in mice. Previous studies have been reported that Catsper3 and Catsper4 knockout male mice were completely infertile due to a quick loss of motility and a lack of hyperactivated motility under capacitating conditions. These data demonstrate that both CATSPER3 and CATSPER4 are required for hyperactivated sperm motility during capacitation and for male fertility. The CATSPER channel may also be an excellent drug target for male contraceptives.

Function of CATSPER3 Membrane Protein

The sperm motility defects in Catsper3^−/− and Catsper4^−/− mice are very similar to those seen in Catsper1^−/− and Catsper2^−/− mice. Lack of any of the four CATSPER proteins appears to result in deficiency in hyperactivated motility and quick loss of initial motility in the capacitating conditions. An almost identical phenotype in mice lacking either of the four CATSPER channel proteins, their highly homologous domain structure, and their similar localization to the sperm flagellum all suggest that CATSPERs 1-4 form a tetramer cation channel, which is required for the development of hyperactivated motility during sperm capacitation in the female reproductive tract. Recently report also introduce that the four CATSPER proteins are indeed associated with each other and form a tetramer. In addition, similar sperm motility defects in the Catsper3 and Catsper4 knockout mice are also reported.

Fig.1 Topology of the CatSper channels. (a) Topology diagram of CatSper1 protein based on Ren et al. (b) Topology diagram of CatSper2, 3 and 4 proteins. (Lobley, 2003)

Application of CATSPER3 Membrane Protein in Literature

1. Kim C.W., et al. H₂O₂-induced up-regulation of CatSper3 in mouse brain. Mol Reprod Dev. 2010, 77(8):650-650. PubMed ID: 20586097
   
   

   The study found that CatSper3 is not only expressed in sperm or testis, but also in the brain of mice. And the data suggests that CatSper3 may be a potential target for ROS regulation.

2. Jin J.L., et al. Catsper3 and catsper4 encode two cation channel-like proteins exclusively expressed in the testis. Biol Reprod. 2005, 73(6):1235-1242. PubMed ID: 16107607
   
   

   This article indicates that CATSPER3 and CATSPER4 are two cation-channel proteins and have roles in acrosome reaction and male fertility.

3. Lobley A., et al. Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis. Reprod Biol Endocrinol. 2003, 1(1):53-53. PubMed ID: 12932298
   
   

   All four of the CatSper proteins are predicted to contain a common coiled-coil protein-protein interaction domain in their C-terminal tail, which leads to the hypothesis that the CatSper proteins form a functional hetero-tetrameric channel in sperm.

4. Qi H., et al. All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc Natl Acad Sci U S A. 2007, 104(4):1219-1223. PubMed ID: 17227845
   
   

   These results indicate that targeted disruption of murine CatSper3 or CatSper4 also abrogated ICatSper, sperm cell hyperactivated motility and male fertility but did not affect spermatogenesis or initial motility. Direct protein interactions among CatSpers, the sperm specificity of these proteins, and loss of ICatSper in each of the four CatSper^-/- mice indicate that CatSpers are highly specialized flagellar proteins.

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Reference

1. Lobley A, et al. (2003). Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis. Reprod Biol Endocrinol. 1(1), 53-53.

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