Identical phenotypes of CatSper1 and CatSper2 null sperm

被引:146
作者
Carlson, AE
Quill, TA
Westenbroek, RE
Schuh, SM
Hille, B
Babcock, DF
机构
[1] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA
[2] Univ Texas, SW Med Ctr, Cecil H & Ida Green Ctr Reprod Biol Sci, Dept Pharmacol, Dallas, TX 75390 USA
[3] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA
关键词
D O I
10.1074/jbc.M501430200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Among several candidate Ca2+ 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 Ca2+ entry. Here we show that failure of hyperactivation of CatSper2 null sperm similarly correlates with an absence of depolarization-evoked Ca2+ entry. Additional shared aspects of the phenotypes of CatSper1 and -2 null sperm include unperturbed regional distributions of conventional voltage-gated Ca2+ 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 Ca2+ messenger rather than by preventing flagellar responses to Ca2+. 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.
引用
收藏
页码:32238 / 32244
页数:7
相关论文
共 46 条
  • [1] CATSPER2, a human autosomal nonsyndromic male infertility gene
    Avidan, N
    Tamary, H
    Dgany, O
    Cattan, D
    Pariente, A
    Thulliez, M
    Borot, N
    Moati, L
    Barthelme, A
    Shalmon, L
    Krasnov, T
    Asher, EB
    Olender, T
    Khen, M
    Yaniv, I
    Zaizov, R
    Shalev, H
    Delaunay, J
    Fellous, M
    Lancet, D
    Beckmann, JS
    [J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2003, 11 (07) : 497 - 502
  • [2] BABCOCK DF, 1987, J BIOL CHEM, V262, P15041
  • [3] Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3
    Biel, M
    Seeliger, M
    Pfeifer, A
    Kohler, K
    Gerstner, A
    Ludwig, A
    Jaissle, G
    Fauser, S
    Zrenner, E
    Hofmann, F
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) : 7553 - 7557
  • [5] CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm
    Carlson, AE
    Westenbroek, RE
    Quill, T
    Ren, DJ
    Clapham, DE
    Hille, B
    Garbers, DL
    Babcock, DF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (25) : 14864 - 14868
  • [6] Abnormal coronary function in mice deficient in α1H T-type Ca2+ channels
    Chen, CC
    Lamping, KG
    Nuno, DW
    Barresi, R
    Prouty, SJ
    Lavoie, JL
    Cribbs, LL
    England, SK
    Sigmund, CD
    Weiss, RM
    Williamson, RA
    Hill, JA
    Campbell, KP
    [J]. SCIENCE, 2003, 302 (5649) : 1416 - 1418
  • [7] THE ONSET AND MAINTENANCE OF HYPERACTIVATED MOTILITY OF SPERMATOZOA FROM THE MOUSE
    COOPER, TG
    [J]. GAMETE RESEARCH, 1984, 9 (01): : 55 - 74
  • [8] DOMINO SE, 1991, METHOD ENZYMOL, V195, P345
  • [9] Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect
    Esposito, G
    Jaiswal, BS
    Xie, F
    Krajnc-Franken, MAM
    Robben, TJAA
    Strik, AM
    Kuil, C
    Philipsen, RLA
    van Duin, M
    Conti, M
    Gossen, JA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) : 2993 - 2998
  • [10] FRASER LR, 1982, J ANDROL, V3, P412