CATSPER1 Membrane Protein Introduction

Introduction of CATSPER1

CATSPER is a cation channel exclusively detected in sperm cells and located in the plasma membrane of the principal piece of the flagellum. CATSPER comprises a 4-protein family forming a tetrameric channel (CATSPER). The 4-member family associates with accessory proteins (CATSPERβ, CATSPERγ, and CATSPERδ). This channel mediates Ca²⁺ entry necessary for the hyperactivation motility and fertility since it is required to penetrate the zona pellucida surrounding the oocyte7. The four subunits are expressed at different stages of spermatogenesis. While Catsper1, 3 and 4 are transcribed in spermatids, indicating common transcriptional regulation, Catsper 2 is found in pachytene spermatocytes. The Catsper1 gene is the first discovered in this family and differs from the other familial genes in its histidine-rich cytoplasmic domain, which senses changes in intracellular pH and activates the CATSPER channel. However, the disruption of any of the four Catsper genes results in a nonfunctional channel leading to deficient hyperactivation motility and male infertility.

Function of CATSPER1 Membrane Protein

CatSper, a cation channel of sperm, is a pH gated channel and consists of four pore-forming proteins (CatSper1-4). The alkaline environment of the female reproduction tract activates the CatSper channels. The opening of these channels increases the intracellular Ca²⁺ concentration and consequently hyper-activates sperm. Hyper-activation, a type of asymmetric motility, is vital for fertility and impairment in the function of the CatSper channels and its related genes will disturb fertility in both human and animal.

Fig.1 Diagram of ion fluxes and signaling events of mammalian sperm capacitation. (Darszon, 2006)

Application of CATSPER1 Membrane Protein in Literature

1. Soleimani M.Z., et al. Alteration in CatSper1 and 2 genes expression, sperm parameters and testis histology in varicocelized rats. Int J Reprod Biomed (Yazd). 2018, 16(3): 183–190. PubMed ID: 29766149
   
   

   This study indicated that experimental varicocele has adverse effects on sperm parameters, testis structure and the expression of CatSper1 and 2 genes.

2. Carlson A.E., et al. CatSper1 required for evoked Ca²⁺ entry and control of flagellar function in sperm. Proc Natl Acad Sci U S A. 2003, 100(25):14864-14868. PubMed ID: 14657352
   
   

   This article indicates that the proposed role of CatSper1 as the route for an entry of Ca²⁺ that is required for hyperactivated motility in the preparation of sperm for fertilization. These results suggest that the CatSper ion channel proteins are attractive targets in the development of new nonhormonal contraceptives and improved methods for screening and treatment of male infertility.

3. Jimenez-Badillo S.E., et al. Catsper1 promoter is bidirectional and regulates the expression of a novel lncRNA. Sci Rep. 2017, 7(1):13351. PubMed ID: 29042633
   
   

   In this study, authors find that the Catsper1 promoter has in vitro transcriptional activity in either orientation in GC-1 spg mouse spermatogonial cells. The results also show that this promoter regulates the expression of a new divergent Catsper1 gene named Catsper1au (Catsper1 antisense upstream transcript). The analysis of the 1402 bp whole genome sequence reveals that Catsper1au is an intronless and polyadenylated lncRNA, located in the nuclei of Sertoli and spermatogenic cells from adult testis. These data indicate that Catsper1au is divergently expressed from the Catsper1 promoter and could regulate gene expression during spermatogenesis.

4. Mannowetz N., et al. Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids. Proc Natl Acad Sci U S A. 2017, 114(22):5743-5748. PubMed ID: 28507119
   
   

   These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

5. Zou Q.X., et al. Diethylstilbestrol activates CatSper and disturbs progesterone actions in human spermatozoa. Hum Reprod. 2017, 32(2):290-298. PubMed ID: 28031325
   
   

   This report indicates that diethylstilbestrol (DES) can disturb progesterone actions on human spermatozoa, but this study was performed in vitro, and caution must be taken when extrapolating the results in practical applications.

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Reference

1. Darszon A, et al. (2006). Sperm channel diversity and functional multiplicity. Reproduction. 131(6), 977-988.

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