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Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis.

Lobley A, Pierron V, Reynolds L, Allen L, Michalovich D - Reprod. Biol. Endocrinol. (2003)

Bottom Line: However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Target Discovery, Inpharmatica Ltd, 60 Charlotte Street, London W1T 2NU, UK. a.lobley@inpharmatica.co.uk

ABSTRACT

Background: CatSper1 and CatSper2 are two recently identified channel-like proteins, which show sperm specific expression patterns. Through targeted mutagenesis in the mouse, CatSper1 has been shown to be required for fertility, sperm motility and for cAMP induced Ca2+ current in sperm. Both channels resemble a single pore forming repeat from a four repeat voltage dependent Ca2+ /Na+ channel. However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction. As the pore forming units of voltage gated cation channels form a tetramer it has been suggested that the known CatSper proteins require additional subunits and/or interaction partners to function.

Results: Using in silico gene identification and prediction techniques, we have identified two further members of the CatSper family, CatSper3 and Catsper4. Each carries a single channel-forming domain with the predicted pore-loop containing the consensus sequence TxDxW. Each of the new CatSper genes has evidence for expression in the testis. Furthermore we identified coiled-coil protein-protein interaction domains in the C-terminal tails of each of the CatSper channels, implying that CatSper channels 1,2,3 and 4 may interact directly or indirectly to form a functional tetramer.

Conclusions: The topological and sequence relationship of CatSper1 and CatSper2 to the four repeat Ca2+ /Na+ channels suggested other members of this family may exist. We have identified a further two novel CatSper genes, conserved in both the human and mouse genomes. 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.

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Genomic organisation of the human and mouse CatSper4 genes. (a) Gene structure of human and mouse CatSper4 genes on human chromosome 1p35.3 and mouse chromosome 4 band D3 respectively. Horizontal line represent human genome assembly NCBI 31 and mouse genome assembly NCBI 03, filled boxes represent coding regions, un-filled boxes represent non-coding regions. (b) Comparison of exon boundaries between human and mouse genes, exons are shaded alternately. Predicted transmembrane regions are underlined, the pore forming region is underlined with a dashed line.
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Figure 2: Genomic organisation of the human and mouse CatSper4 genes. (a) Gene structure of human and mouse CatSper4 genes on human chromosome 1p35.3 and mouse chromosome 4 band D3 respectively. Horizontal line represent human genome assembly NCBI 31 and mouse genome assembly NCBI 03, filled boxes represent coding regions, un-filled boxes represent non-coding regions. (b) Comparison of exon boundaries between human and mouse genes, exons are shaded alternately. Predicted transmembrane regions are underlined, the pore forming region is underlined with a dashed line.

Mentions: The human CatSper4 gene is predicted to span a region of 12 kb and be comprised of 10 coding exons, (Figure 2a and Table 3). Human CatSper4 is only partially represented by a single EST originating from a testis library. In contrast mouse CatSper4 is present in the databases as a RIKEN testis derived cDNA (AK077145) [18] and is also represented by ten ESTs, all of which are either testis derived or derived from a pooled library containing testis material.


Identification of human and mouse CatSper3 and CatSper4 genes: characterisation of a common interaction domain and evidence for expression in testis.

Lobley A, Pierron V, Reynolds L, Allen L, Michalovich D - Reprod. Biol. Endocrinol. (2003)

Genomic organisation of the human and mouse CatSper4 genes. (a) Gene structure of human and mouse CatSper4 genes on human chromosome 1p35.3 and mouse chromosome 4 band D3 respectively. Horizontal line represent human genome assembly NCBI 31 and mouse genome assembly NCBI 03, filled boxes represent coding regions, un-filled boxes represent non-coding regions. (b) Comparison of exon boundaries between human and mouse genes, exons are shaded alternately. Predicted transmembrane regions are underlined, the pore forming region is underlined with a dashed line.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC184451&req=5

Figure 2: Genomic organisation of the human and mouse CatSper4 genes. (a) Gene structure of human and mouse CatSper4 genes on human chromosome 1p35.3 and mouse chromosome 4 band D3 respectively. Horizontal line represent human genome assembly NCBI 31 and mouse genome assembly NCBI 03, filled boxes represent coding regions, un-filled boxes represent non-coding regions. (b) Comparison of exon boundaries between human and mouse genes, exons are shaded alternately. Predicted transmembrane regions are underlined, the pore forming region is underlined with a dashed line.
Mentions: The human CatSper4 gene is predicted to span a region of 12 kb and be comprised of 10 coding exons, (Figure 2a and Table 3). Human CatSper4 is only partially represented by a single EST originating from a testis library. In contrast mouse CatSper4 is present in the databases as a RIKEN testis derived cDNA (AK077145) [18] and is also represented by ten ESTs, all of which are either testis derived or derived from a pooled library containing testis material.

Bottom Line: However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Target Discovery, Inpharmatica Ltd, 60 Charlotte Street, London W1T 2NU, UK. a.lobley@inpharmatica.co.uk

ABSTRACT

Background: CatSper1 and CatSper2 are two recently identified channel-like proteins, which show sperm specific expression patterns. Through targeted mutagenesis in the mouse, CatSper1 has been shown to be required for fertility, sperm motility and for cAMP induced Ca2+ current in sperm. Both channels resemble a single pore forming repeat from a four repeat voltage dependent Ca2+ /Na+ channel. However, neither CatSper1 or CatSper2 have been shown to function as cation channels when transfected into cells, singly or in conjunction. As the pore forming units of voltage gated cation channels form a tetramer it has been suggested that the known CatSper proteins require additional subunits and/or interaction partners to function.

Results: Using in silico gene identification and prediction techniques, we have identified two further members of the CatSper family, CatSper3 and Catsper4. Each carries a single channel-forming domain with the predicted pore-loop containing the consensus sequence TxDxW. Each of the new CatSper genes has evidence for expression in the testis. Furthermore we identified coiled-coil protein-protein interaction domains in the C-terminal tails of each of the CatSper channels, implying that CatSper channels 1,2,3 and 4 may interact directly or indirectly to form a functional tetramer.

Conclusions: The topological and sequence relationship of CatSper1 and CatSper2 to the four repeat Ca2+ /Na+ channels suggested other members of this family may exist. We have identified a further two novel CatSper genes, conserved in both the human and mouse genomes. 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.

Show MeSH
Related in: MedlinePlus