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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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Topology diagram for the L-type and T-type four repeat voltage gated calcium channel families.
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Figure 9: Topology diagram for the L-type and T-type four repeat voltage gated calcium channel families.

Mentions: The CatSper ion channel subunits are distant in sequence relationship; sequence identity ranges between 21.6% and 26.5% across the ion transport domain (Table 6). This low sequence identity is in contrast with that observed for the voltage-gated sodium and calcium channel families. Calcium L-type calcium channels generally share ~25% sequence identity over full their length sequence and upwards of 75% sequence identity between their corresponding ion-transport repeat regions (Table 7). These observations are further supported by the phylogenetic tree (Figure 8) which shows that each repeat is more closely related to its analogous repeat in a paralagoue than to the other repeats in the same gene unit, i.e. repeat I in alpha 1S is more closely related to repeat I in alpha 1T than to repeat II in alpha 1S. Figure 9 shows the repeat topology of a voltage-gated cation channel. In addition, repeats 1 and 3, and repeats 2 and 4 share common ancestry with all four repeats stemming from a single common ancestor (Figure 8). In contrast, the CatSper family members do not associate with any one particular repeat, this therefore raises questions over the detailed evolutionary history of the CatSper family.


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)

Topology diagram for the L-type and T-type four repeat voltage gated calcium channel families.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Topology diagram for the L-type and T-type four repeat voltage gated calcium channel families.
Mentions: The CatSper ion channel subunits are distant in sequence relationship; sequence identity ranges between 21.6% and 26.5% across the ion transport domain (Table 6). This low sequence identity is in contrast with that observed for the voltage-gated sodium and calcium channel families. Calcium L-type calcium channels generally share ~25% sequence identity over full their length sequence and upwards of 75% sequence identity between their corresponding ion-transport repeat regions (Table 7). These observations are further supported by the phylogenetic tree (Figure 8) which shows that each repeat is more closely related to its analogous repeat in a paralagoue than to the other repeats in the same gene unit, i.e. repeat I in alpha 1S is more closely related to repeat I in alpha 1T than to repeat II in alpha 1S. Figure 9 shows the repeat topology of a voltage-gated cation channel. In addition, repeats 1 and 3, and repeats 2 and 4 share common ancestry with all four repeats stemming from a single common ancestor (Figure 8). In contrast, the CatSper family members do not associate with any one particular repeat, this therefore raises questions over the detailed evolutionary history of the CatSper family.

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