CATSPER4 Membrane Protein Introduction

Introduction of CATSPER4

Calciumions play a primary role in the regulation of sperm cell behavior. Recent researches found a voltage-gatedion channel (CatSper) that was expressed in male germ cells but not in other cells. The putative channel contains 6 transmembrane segments, making it more similar to the voltage-gated potassium channels, but the ion selectivity pore domain sequence resembles that of a Ca(v) channel. The mRNA is expressed during the meiotic or postmeiotic stages of spermatogenesis, and the protein is localized to the sperm flagellum, suggesting a role in the regulation of sperm motility. The mRNA for the channel is present in mouse, rat, and human sperm cells, and the gene is found on chromosome 2 E5-F1 in the mouse and 15q13 in the human.

Basic Information of CATSPER4
Protein Name	Cation channel sperm-associated protein 4
Gene Name	CATSPER4
Aliases	CatSper4
Organism	Homo sapiens (Human)
UniProt ID	Q7RTX7
Transmembrane Times	6
Length (aa)	472
Sequence	MRDNEKAWWQQWTSHTGLEGWGGTQEDRMGFGGAVAALRGRPSPLQSTIHESYGRPEEQVLINRQEITNKADAWDMQEFITHMYIKQLLRHPAFQLLLALLLVINAITIALRTNSYLDQKHYELFSTIDDIVLTILLCEVLLGWLNGFWIFWKDGWNILNFIIVFILLLRFFINEINIPSINYTLRALRLVHVCMAVEPLARIIRVILQSVPDMANIMVLILFFMLVFSVFGVTLFGAFVPKHFQNIQVALYTLFICITQDGWVDIYSDFQTEKREYAMEIGGAIYFTIFITIGAFIGINLFVIVVTTNLEQMMKAGEQGQQQRITFSETGAEEEEENDQLPLVHCVVARSEKSGLLQEPLAGGPLSNLSENTCDNFCLVLEAIQENLRQYKEIRDELNMIVEEVRAIRFNQEQESEVLNRRSSTSGSLETTSSKDIRQMSQQQDLLSALVSMEKVHDSSSQILLKKHKSSH

Function of CATSPER4 Membrane Protein

Targeted disruption of CatSper1-4 genes in mouse lead to complete loss of ICatSper and identical phenotype of male infertility indicates that all pore forming CatSper α subunits are essential for a functional channel. CatSper δ knockout results in complete loss of CatSper currents and male infertility. Patch clamp recordings of mouse spermatozoa have revealed the origin of ICatSper from the principal piece that corresponds to antibody localization of the CatSper protein. ICatSper increases intracellular Ca²⁺ concentrations that eventually leads to hyperactivated motility.

CATSPER4 Membrane Protein Introduction Fig.1 Theoretical model for the formation of a CatSper hetero-terameric channel. (Lobley, 2003)

Application of CATSPER4 Membrane Protein in Literature

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. PubMed ID: 12932298

The topological and sequence relationship of CatSper1 and CatSper2 to the four repeat Ca²⁺ /Na⁺ channels suggested that other members of this family may exist. Furthermore, all four of the CatSper proteins are predicted to contain a common coiled-coil protein-protein interaction domain in their C-terminal tail. Coupled with expression data, this leads to the hypothesis that the CatSper proteins form a functional hetero-tetrameric channel in sperm.
Rezaian J., et al. CatSper genes expression, semen characteristics and histology of testes in the contusive spinal cord-injured mice model. Spinal Cord. 2009, 47(1):76-81. PubMed ID: 18607386

This present study demands a revisit to the idiopathic male infertility patients who show normal sperm counts and normal initial motility for defects in sperm hyperactivated motility and for potential CATSPER gene mutations. The CATSPER channel also may be an excellent drug target for male contraceptives.
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: 24969054

These results suggest that CATSPER3 and CATSPER4 are two cation-channel proteins and have roles in acrosome reaction and male fertility.

CATSPER4 Preparation Options

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Reference

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.

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