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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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Multiple sequence alignment of the CatSper ion channel family ion-transport domain. Transmembrane regions are underlined in black and the S4 voltage sensor transmembrane helix is highlighted in red. The channel pore consensus sequence motif is boxed in blue. Genbank accession codes for the published Catsper genes are as follows: MSper1 AF407332, HSper1 AF407333, MSper2 AF411816, HSper2v1 AF411817, HSper2v2 AF411818, HSper2v3 AF411819.
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Figure 5: Multiple sequence alignment of the CatSper ion channel family ion-transport domain. Transmembrane regions are underlined in black and the S4 voltage sensor transmembrane helix is highlighted in red. The channel pore consensus sequence motif is boxed in blue. Genbank accession codes for the published Catsper genes are as follows: MSper1 AF407332, HSper1 AF407333, MSper2 AF411816, HSper2v1 AF411817, HSper2v2 AF411818, HSper2v3 AF411819.

Mentions: Ion specificity is determined by a pore consensus sequence [T/S] × [D/E] × W in voltage gated Calcium channels [22]. Sequence analysis of this region in the CatSpers highlights the presence of a similar conserved motif T×D×W (Figure 5 and 6b) suggesting that the CatSper ion channels may be selective for calcium ions, as previously discussed for CatSper1 [5]. BLASTP homology searches also link the CatSpers most closely with the T-type Calcium channels.


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)

Multiple sequence alignment of the CatSper ion channel family ion-transport domain. Transmembrane regions are underlined in black and the S4 voltage sensor transmembrane helix is highlighted in red. The channel pore consensus sequence motif is boxed in blue. Genbank accession codes for the published Catsper genes are as follows: MSper1 AF407332, HSper1 AF407333, MSper2 AF411816, HSper2v1 AF411817, HSper2v2 AF411818, HSper2v3 AF411819.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Multiple sequence alignment of the CatSper ion channel family ion-transport domain. Transmembrane regions are underlined in black and the S4 voltage sensor transmembrane helix is highlighted in red. The channel pore consensus sequence motif is boxed in blue. Genbank accession codes for the published Catsper genes are as follows: MSper1 AF407332, HSper1 AF407333, MSper2 AF411816, HSper2v1 AF411817, HSper2v2 AF411818, HSper2v3 AF411819.
Mentions: Ion specificity is determined by a pore consensus sequence [T/S] × [D/E] × W in voltage gated Calcium channels [22]. Sequence analysis of this region in the CatSpers highlights the presence of a similar conserved motif T×D×W (Figure 5 and 6b) suggesting that the CatSper ion channels may be selective for calcium ions, as previously discussed for CatSper1 [5]. BLASTP homology searches also link the CatSpers most closely with the T-type Calcium channels.

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