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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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Un-rooted phylogenetic tree showing CatSper family members with selected T- and L-type calcium channels. Repeats 1–4 of selected human L- and T-type calcium channels; CCAA_Human – calcium channel alpha1A (SWISSPROT O00555), CCAC_Human – calcium channel alpha1C (SWISSPROT Q13936), CCAG_Human – calcium channel alpha1G (SWISSPROT O43497), CCAH_Human – calcium channel 1H (SWISSPROT O95180) and CCAS_Human – calcium channel alpha1S (SWISSPROT Q13698).
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Figure 8: Un-rooted phylogenetic tree showing CatSper family members with selected T- and L-type calcium channels. Repeats 1–4 of selected human L- and T-type calcium channels; CCAA_Human – calcium channel alpha1A (SWISSPROT O00555), CCAC_Human – calcium channel alpha1C (SWISSPROT Q13936), CCAG_Human – calcium channel alpha1G (SWISSPROT O43497), CCAH_Human – calcium channel 1H (SWISSPROT O95180) and CCAS_Human – calcium channel alpha1S (SWISSPROT Q13698).

Mentions: The phylogenetic tree shown in figure 8 was constructed from sequence alignments of the CatSper protein family with calcium channel sequences CCAA_HUMAN, CCAH_HUMAN, CCAG_HUMAN, CCAS_HUMAN, CCAC_HUMAN over the ion-transport domain region. PHYLIP [16] PROT-PARS maximum parsimony programme was used to build 1000 bootstrap trees from the sequence alignment. The final tree was obtained using the CONSENSE programme to select the best tree by majority rule.


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)

Un-rooted phylogenetic tree showing CatSper family members with selected T- and L-type calcium channels. Repeats 1–4 of selected human L- and T-type calcium channels; CCAA_Human – calcium channel alpha1A (SWISSPROT O00555), CCAC_Human – calcium channel alpha1C (SWISSPROT Q13936), CCAG_Human – calcium channel alpha1G (SWISSPROT O43497), CCAH_Human – calcium channel 1H (SWISSPROT O95180) and CCAS_Human – calcium channel alpha1S (SWISSPROT Q13698).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Un-rooted phylogenetic tree showing CatSper family members with selected T- and L-type calcium channels. Repeats 1–4 of selected human L- and T-type calcium channels; CCAA_Human – calcium channel alpha1A (SWISSPROT O00555), CCAC_Human – calcium channel alpha1C (SWISSPROT Q13936), CCAG_Human – calcium channel alpha1G (SWISSPROT O43497), CCAH_Human – calcium channel 1H (SWISSPROT O95180) and CCAS_Human – calcium channel alpha1S (SWISSPROT Q13698).
Mentions: The phylogenetic tree shown in figure 8 was constructed from sequence alignments of the CatSper protein family with calcium channel sequences CCAA_HUMAN, CCAH_HUMAN, CCAG_HUMAN, CCAS_HUMAN, CCAC_HUMAN over the ion-transport domain region. PHYLIP [16] PROT-PARS maximum parsimony programme was used to build 1000 bootstrap trees from the sequence alignment. The final tree was obtained using the CONSENSE programme to select the best tree by majority rule.

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