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Published in: Reproductive Biology and Endocrinology 1/2003

Open Access 01-12-2003 | Research

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

Authors: Anna Lobley, Valerie Pierron, Lindsey Reynolds, Liz Allen, David Michalovich

Published in: Reproductive Biology and Endocrinology | Issue 1/2003

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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 T×D×W. 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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Literature
1.
go back to reference Serrano CJ, Trevino CL, Felix R, Darszon A: Voltage-dependent Ca(2+) channel subunit expression and immunolocalization in mouse spermatogenic cells and sperm. FEBS Lett. 1999, 462: 171-176. 10.1016/S0014-5793(99)01518-5.CrossRefPubMed Serrano CJ, Trevino CL, Felix R, Darszon A: Voltage-dependent Ca(2+) channel subunit expression and immunolocalization in mouse spermatogenic cells and sperm. FEBS Lett. 1999, 462: 171-176. 10.1016/S0014-5793(99)01518-5.CrossRefPubMed
2.
go back to reference Westenbroek RE, Babcock DF: Discrete regional distributions suggest diverse functional roles of calcium channel alpha1 subunits in sperm. Dev Biol. 1999, 207: 457-69. 10.1006/dbio.1998.9172.CrossRefPubMed Westenbroek RE, Babcock DF: Discrete regional distributions suggest diverse functional roles of calcium channel alpha1 subunits in sperm. Dev Biol. 1999, 207: 457-69. 10.1006/dbio.1998.9172.CrossRefPubMed
3.
go back to reference Wiesner B, Weiner J, Middendorff R, Hagen V, Kaupp UB, Weyand I: Cyclic Nucleotide-gated Channels on the Flagellum Control Ca2+ Entry into Sperm. J Cell Biol. 1998, 142: 473-484. 10.1083/jcb.142.2.473.PubMedCentralCrossRefPubMed Wiesner B, Weiner J, Middendorff R, Hagen V, Kaupp UB, Weyand I: Cyclic Nucleotide-gated Channels on the Flagellum Control Ca2+ Entry into Sperm. J Cell Biol. 1998, 142: 473-484. 10.1083/jcb.142.2.473.PubMedCentralCrossRefPubMed
4.
go back to reference Jungnickel MK, Marrero H, Birnbaumer L, Lemos JR, Florman HM: Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nat Cell Biol. 2001, 3: 499-502. 10.1038/35074570.CrossRefPubMed Jungnickel MK, Marrero H, Birnbaumer L, Lemos JR, Florman HM: Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nat Cell Biol. 2001, 3: 499-502. 10.1038/35074570.CrossRefPubMed
5.
go back to reference Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL, Clapham DE: A sperm ion channel required for sperm motility and male fertility. Nature. 2001, 413: 603-9. 10.1038/35098027.CrossRefPubMed Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL, Clapham DE: A sperm ion channel required for sperm motility and male fertility. Nature. 2001, 413: 603-9. 10.1038/35098027.CrossRefPubMed
6.
go back to reference Quill TA, Ren D, Clapham DE, Garbers DL: A voltage-gated ion channel expressed specifically in spermatozoa. Proc Natl Acad Sci U S A. 2001, 98: 12527-31. 10.1073/pnas.221454998.PubMedCentralCrossRefPubMed Quill TA, Ren D, Clapham DE, Garbers DL: A voltage-gated ion channel expressed specifically in spermatozoa. Proc Natl Acad Sci U S A. 2001, 98: 12527-31. 10.1073/pnas.221454998.PubMedCentralCrossRefPubMed
8.
go back to reference Altschul SF, Madden TL, Schaffer AA, Zhang J, Anang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucl Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.PubMedCentralCrossRefPubMed Altschul SF, Madden TL, Schaffer AA, Zhang J, Anang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucl Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.PubMedCentralCrossRefPubMed
9.
go back to reference Burge C, Karlin S: Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997, 268: 78-94. 10.1006/jmbi.1997.0951.CrossRefPubMed Burge C, Karlin S: Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997, 268: 78-94. 10.1006/jmbi.1997.0951.CrossRefPubMed
12.
go back to reference Lobenhofer EK, Bennett L, Cable PL, Li L, Bushel PR, Afshari CA: Regulation of DNA replication fork genes by 17beta-estradiol. Mol Endocrinol. 2002, 16: 1215-1229. 10.1210/me.16.6.1215.PubMed Lobenhofer EK, Bennett L, Cable PL, Li L, Bushel PR, Afshari CA: Regulation of DNA replication fork genes by 17beta-estradiol. Mol Endocrinol. 2002, 16: 1215-1229. 10.1210/me.16.6.1215.PubMed
13.
go back to reference Krogh A, Larsson B, von Heijne G, Sonnhammer EL: Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol. 2001, 305: 567-580. 10.1006/jmbi.2000.4315.CrossRefPubMed Krogh A, Larsson B, von Heijne G, Sonnhammer EL: Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol. 2001, 305: 567-580. 10.1006/jmbi.2000.4315.CrossRefPubMed
14.
go back to reference Lupas A, Van Dyke M, Stock J: Predicting Coiled Coils from Protein Sequences. Science. 1991, 252: 1162-1164.CrossRefPubMed Lupas A, Van Dyke M, Stock J: Predicting Coiled Coils from Protein Sequences. Science. 1991, 252: 1162-1164.CrossRefPubMed
15.
go back to reference Thompson JD, Higgins DG, Gibson TJ: CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22: 4673-4680.PubMedCentralCrossRefPubMed Thompson JD, Higgins DG, Gibson TJ: CLUSTALW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22: 4673-4680.PubMedCentralCrossRefPubMed
17.
go back to reference Felsenstein J: PHYLIP – Phylogeny Inference Package (Version 3.2). Cladistics. 1989, 5: 164-166. Felsenstein J: PHYLIP – Phylogeny Inference Package (Version 3.2). Cladistics. 1989, 5: 164-166.
18.
go back to reference Adachi J, Aizawa K, Akahira S, Akimura T, Arai A, Aono H, Arakawa T, Bono H, Carninci P, Fukuda S: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002, 420: 563-573. 10.1038/nature01266.CrossRefPubMed Adachi J, Aizawa K, Akahira S, Akimura T, Arai A, Aono H, Arakawa T, Bono H, Carninci P, Fukuda S: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002, 420: 563-573. 10.1038/nature01266.CrossRefPubMed
19.
go back to reference Lim S, Jin K, Friedman E: Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha. J Biol Chem. 2002, 277: 25040-25046. 10.1074/jbc.M203257200.CrossRefPubMed Lim S, Jin K, Friedman E: Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha. J Biol Chem. 2002, 277: 25040-25046. 10.1074/jbc.M203257200.CrossRefPubMed
21.
go back to reference Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S: Structural parts involved in activation and inactivation of the sodium channel. Nature. 1989, 339: 597-603. 10.1038/339597a0.CrossRefPubMed Stuhmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S: Structural parts involved in activation and inactivation of the sodium channel. Nature. 1989, 339: 597-603. 10.1038/339597a0.CrossRefPubMed
22.
go back to reference Ellinor PT, Yang J, Sather WA, Zhang JF, Tsien RW: Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. Neuron. 1995, 15: 1121-32.CrossRefPubMed Ellinor PT, Yang J, Sather WA, Zhang JF, Tsien RW: Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. Neuron. 1995, 15: 1121-32.CrossRefPubMed
23.
go back to reference White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH: Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998, 396: 629-630. 10.1038/25248.CrossRef White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH: Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998, 396: 629-630. 10.1038/25248.CrossRef
24.
go back to reference Kammerer RA, Frank S, Schulthess T, Landwehr R, Lustig A, Engel J: Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. Biochemistry. 1999, 38: 13263-13269. 10.1021/bi991018t.CrossRefPubMed Kammerer RA, Frank S, Schulthess T, Landwehr R, Lustig A, Engel J: Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. Biochemistry. 1999, 38: 13263-13269. 10.1021/bi991018t.CrossRefPubMed
25.
go back to reference Sutton RB, Fasshauer D, Jahn R, Brunger AT: Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature. 1998, 395: 347-53. 10.1038/26412.CrossRefPubMed Sutton RB, Fasshauer D, Jahn R, Brunger AT: Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature. 1998, 395: 347-53. 10.1038/26412.CrossRefPubMed
26.
go back to reference Benoff S: Voltage dependent calcium channels in mammalian spermatozoa. Front Biosci. 1998, 3: D1220-40.PubMed Benoff S: Voltage dependent calcium channels in mammalian spermatozoa. Front Biosci. 1998, 3: D1220-40.PubMed
Metadata
Title
Identification of human and mouse CatSper3 and CatSper4 genes: Characterisation of a common interaction domain and evidence for expression in testis
Authors
Anna Lobley
Valerie Pierron
Lindsey Reynolds
Liz Allen
David Michalovich
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2003
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-1-53

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