• PMID: 16036917
• Gene Name: CATSPER2
• Condition: Infertility
• Association: The findings suggest that the expression of Catsper 1& 2 are co-dependent and dictates identical loss-of-function sperm phenotypes
• Sex: Male
• Infertility type: Male infertility

Identical phenotypes of CatSper1 and CatSper2 null sperm

Carlson AE, Quill TA, Westenbroek RE, Schuh SM, Hille B, Babcock DF.

Among several candidate Ca(2+) entry channels in sperm, only CatSper1 and CatSper2 are known to have required roles in male fertility. Past work with CatSper1 null sperm indicates that a critical lesion in hyperactivated motility underlies the infertility phenotype and is associated with an absence of depolarization-evoked Ca(2+)entry. Here we show that failure of hyperactivation of CatSper2 null sperm similarly correlates with an absence of depolarization evoked Ca(2+) entry. Additional shared aspects of the phenotypes of CatSper1 and -2 null sperm include unperturbed regional distributions of conventional voltage-gated Ca(2+) channel proteins and robust acceleration of the flagellar beat by bicarbonate. Further study reveals that treatment of both wild-type and CatSper2 null sperm with procaine increases beat asymmetry, a characteristic of the flagellar waveform of hyperactivation. This partial rescue of the loss-of-hyperactivation phenotype suggests that an absence of CatSper2 precludes hyperactivation by preventing delivery of needed Ca(2+) messenger rather than by preventing flagellar responses to Ca(2+). CatSper2 null sperm also have an increased basal cAMP content and beat frequency. Protein kinase A inhibitor H89 lowers beat frequency to that of wild-type sperm, suggesting that CatSper2 is required for protein kinase A-mediated, tonic control of resting cAMP content. Relative to wild-type testis, CatSper1 and -2 null testes contain normal amounts of CatSper2 and -1 transcripts, respectively. However, CatSper1 null sperm lack CatSper2 protein and CatSper2 null sperm lack CatSper1 protein. Hence, stable expression of CatSper1 protein requires CatSper2 and vice versa. This co-dependent expression dictates identical loss-of-function sperm phenotypes for CatSper1 and -2 null mutants. FAU - Carlson, Anne E AU - Carlson AE AD - Department of Physiology and Biophysics, University of Washington, Seattle, 98195, USA. FAU - Quill, Timothy A AU - Quill TA FAU - Westenbroek, Ruth E AU - Westenbroek RE FAU - Schuh, Sonya M AU - Schuh SM FAU - Hille, Bertil AU - Hille B