Molecular Human Reproduction, Vol. 5, No. 11, 1017-1026,
November 1999
© 1999 European Society of Human Reproduction and Embryology
Regulation of sperm function |
Regulation of human sperm capacitation by a cholesterol efflux-stimulated signal transduction pathway leading to protein kinase A-mediated up-regulation of protein tyrosine phosphorylation
1 Center for Research on Reproduction and Women's Health, Room 1315, Biomedical Research Building II, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104–6142, and 2 Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, Philadelphia, PA 19104–6080, USA
Abstract
Protein tyrosine phosphorylation is an important intracellular event accompanying the in-vitro capacitation of mouse, bovine and human spermatozoa. Here, we demonstrate that bovine serum albumin (BSA) and NaHCO3 are required for protein tyrosine phosphorylation in ejaculated human spermatozoa. The absence of protein tyrosine phosphorylation in media minus these two constituents could be recovered by addition to the media of cAMP analogues and/or phosphodiesterase inhibitors. Since BSA is postulated to modulate capacitation by removal of cholesterol from the sperm plasma membrane, we determined whether cholesterol release leads to changes in protein tyrosine phosphorylation. Incubation of spermatozoa in media containing BSA resulted in the release of significant amounts of cholesterol when compared with media devoid of BSA. Preloading BSA with cholesterol-SO4 inhibited protein tyrosine phosphorylation, as well as capacitation, and this inhibitory effect was overcome by the addition of dibutyryl cAMP plus isobutylmethylxanthine (IBMX). The functional significance of BSA-mediated cholesterol release, protein tyrosine phosphorylation and capacitation was confirmed by examining the effects of the cholesterol-binding heptasaccharides, methyl-ß-cyclodextrin or OH-propyl-ß-cyclodextrin. Both cyclodextrins caused cholesterol efflux from the spermatozoa, increased protein tyrosine phosphorylation, and stimulated capacitation. Therefore, cholesterol release is associated with the activation of a signal transduction pathway involving protein kinase A and tyrosine kinase second messenger systems, and resulting in protein tyrosine phosphorylation and capacitation.
cAMP/cholesterol/cyclodextrins/human sperm capacitation/protein tyrosine phosphorylation
Notes
3 Current address: Center for Reproductive Endocrinology, 95 Mount Kemble Avenue, Thebaud Building, 2nd Floor, Morristown, NJ 07922, USA
4 To whom correspondence should be addressed
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Muller, P. Muller, G. Pincemy, A. Kurz, and C. Labbe Characterization of Sperm Plasma Membrane Properties after Cholesterol Modification: Consequences for Cryopreservation of Rainbow Trout Spermatozoa Biol Reprod, March 1, 2008; 78(3): 390 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takeo, T. Hoshii, Y. Kondo, H. Toyodome, H. Arima, K.-i. Yamamura, T. Irie, and N. Nakagata Methyl-Beta-Cyclodextrin Improves Fertilizing Ability of C57BL/6 Mouse Sperm after Freezing and Thawing by Facilitating Cholesterol Efflux from the Cells Biol Reprod, March 1, 2008; 78(3): 546 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Edwards, M. G. Buffone, G. R. Knee, M. Rossato, G. Bonanni, S. Masiero, S. Ferasin, G. L. Gerton, S. B. Moss, and C. J. Williams Effects of Extracellular Adenosine 5'-Triphosphate on Human Sperm Motility Reproductive Sciences, October 1, 2007; 14(7): 655 - 666. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Lefievre, K. Bedu-Addo, S. J Conner, G. S M Machado-Oliveira, Y. Chen, J. C Kirkman-Brown, M. A Afnan, S. J Publicover, W C. L Ford, and C. L R Barratt Counting sperm does not add up any more: time for a new equation? Reproduction, April 1, 2007; 133(4): 675 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.N. Jha, A.M. Salicioni, E. Arcelay, O. Chertihin, S. Kumari, J.C. Herr, and P.E. Visconti Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation Mol. Hum. Reprod., December 1, 2006; 12(12): 781 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Grasa, J. A. Cebrian-Perez, and T. Muino-Blanco Signal transduction mechanisms involved in in vitro ram sperm capacitation. Reproduction, November 1, 2006; 132(5): 721 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.P. Burden, C.H. Holmes, R. Persad, and K. Whittington Prostasomes--their effects on human male reproduction and fertility Hum. Reprod. Update, May 1, 2006; 12(3): 283 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Doncel Exploiting common targets in human fertilization and HIV infection: development of novel contraceptive microbicides Hum. Reprod. Update, March 1, 2006; 12(2): 103 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Sleight, P. V. Miranda, N.-W. Plaskett, B. Maier, J. Lysiak, H. Scrable, J. C. Herr, and P. E. Visconti Isolation and Proteomic Analysis of Mouse Sperm Detergent-Resistant Membrane Fractions: Evidence for Dissociation of Lipid Rafts During Capacitation Biol Reprod, October 1, 2005; 73(4): 721 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Kiss, J. Maric, and Y. L. Marcel Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux J. Lipid Res., September 1, 2005; 46(9): 1877 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bedu-Addo, L. Lefievre, F.L.C. Moseley, C.L.R. Barratt, and S.J. Publicover Bicarbonate and bovine serum albumin reversibly 'switch' capacitation-induced events in human spermatozoa Mol. Hum. Reprod., September 1, 2005; 11(9): 683 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. N. Chiu, M.-K. Chung, H.-Y. Tsang, R. Koistinen, H. Koistinen, M. Seppala, K.-F. Lee, and W. S.B. Yeung Glycodelin-S in Human Seminal Plasma Reduces Cholesterol Efflux and Inhibits Capacitation of Spermatozoa J. Biol. Chem., July 8, 2005; 280(27): 25580 - 25589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.L.C. Moseley, K.N. Jha, L. Bjorndahl, I.A. Brewis, S.J. Publicover, C.L.R. Barratt, and L. Lefievre Protein tyrosine phosphorylation, hyperactivation and progesterone-induced acrosome reaction are enhanced in IVF media: an effect that is not associated with an increase in protein kinase A activation Mol. Hum. Reprod., July 1, 2005; 11(7): 523 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G Buffone, J. C Calamera, S. V Verstraeten, and G. F Doncel Capacitation-associated protein tyrosine phosphorylation and membrane fluidity changes are impaired in the spermatozoa of asthenozoospermic patients Reproduction, June 1, 2005; 129(6): 697 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. I. Marin-Briggiler, K. N. Jha, O. Chertihin, M. G. Buffone, J. C. Herr, M. H. Vazquez-Levin, and P. E. Visconti Evidence of the presence of calcium/calmodulin-dependent protein kinase IV in human sperm and its involvement in motility regulation J. Cell Sci., May 1, 2005; 118(9): 2013 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Laflamme, A. Akoum, and P. Leclerc Induction of human sperm capacitation and protein tyrosine phosphorylation by endometrial cells and interleukin-6 Mol. Hum. Reprod., February 1, 2005; 11(2): 141 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Luconi, I. Porazzi, P. Ferruzzi, S. Marchiani, G. Forti, and E. Baldi Tyrosine Phosphorylation of the A Kinase Anchoring Protein 3 (AKAP3) and Soluble Adenylate Cyclase Are Involved in the Increase of Human Sperm Motility by Bicarbonate Biol Reprod, January 1, 2005; 72(1): 22 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Fraire-Zamora and M. T. Gonzalez-Martinez Effect of intracellular pH on depolarization-evoked calcium influx in human sperm Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1688 - C1696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Muratori, I. Porazzi, M. Luconi, S. Marchiani, G. Forti, and E. Baldi Annexin V Binding and Merocyanine Staining Fail to Detect Human Sperm Capacitation J Androl, September 1, 2004; 25(5): 797 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Herrick, P. Bartels, and R. L. Krisher Postthaw Evaluation of In Vitro Function of Epididymal Spermatozoa from Four Species of Free-Ranging African Bovids Biol Reprod, September 1, 2004; 71(3): 948 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Asquith, R. M. Baleato, E. A. McLaughlin, B. Nixon, and R. J. Aitken Tyrosine phosphorylation activates surface chaperones facilitating sperm-zona recognition J. Cell Sci., July 15, 2004; 117(16): 3645 - 3657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shadan, P. S. James, E. A. Howes, and R. Jones Cholesterol Efflux Alters Lipid Raft Stability and Distribution During Capacitation of Boar Spermatozoa Biol Reprod, July 1, 2004; 71(1): 253 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Da Ros, M. J. Munuce, D. J. Cohen, C. I. Marin-Briggiler, D. Busso, P. E. Visconti, and P. S. Cuasnicu Bicarbonate Is Required for Migration of Sperm Epididymal Protein DE (CRISP-1) to the Equatorial Segment and Expression of Rat Sperm Fusion Ability Biol Reprod, May 1, 2004; 70(5): 1325 - 1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mitra and S. Shivaji Novel Tyrosine-Phosphorylated Post-Pyruvate Metabolic Enzyme, Dihydrolipoamide Dehydrogenase, Involved in Capacitation of Hamster Spermatozoa Biol Reprod, April 1, 2004; 70(4): 887 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Minelli, L. Liguori, I. Bellazza, R. Mannucci, B. Johansson, and B. B. Fredholm Involvement of A1 Adenosine Receptors in the Acquisition of Fertilizing Capacity J Androl, March 1, 2004; 25(2): 286 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.G. Buffone, G.F. Doncel, C.I. Marin Briggiler, M.H. Vazquez-Levin, and J.C. Calamera Human sperm subpopulations: relationship between functional quality and protein tyrosine phosphorylation Hum. Reprod., January 1, 2004; 19(1): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Quill, S. A. Sugden, K. L. Rossi, L. K. Doolittle, R. E. Hammer, and D. L. Garbers Hyperactivated sperm motility driven by CatSper2 is required for fertilization PNAS, December 9, 2003; 100(25): 14869 - 14874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Ecroyd, R. C. Jones, and R. J. Aitken Endogenous Redox Activity in Mouse Spermatozoa and Its Role in Regulating the Tyrosine Phosphorylation Events Associated with Sperm Capacitation Biol Reprod, July 1, 2003; 69(1): 347 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.J. de Vries, T. Wiedmer, P.J. Sims, and B.M. Gadella Caspase-Independent Exposure of Aminophospholipids and Tyrosine Phosphorylation in Bicarbonate Responsive Human Sperm Cells Biol Reprod, June 1, 2003; 68(6): 2122 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Nimmo and N. L. Cross Structural Features of Sterols Required to Inhibit Human Sperm Capacitation Biol Reprod, April 1, 2003; 68(4): 1308 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sakkas, G. Leppens-Luisier, H. Lucas, D. Chardonnens, A. Campana, D.R. Franken, and F. Urner Localization of Tyrosine Phosphorylated Proteins in Human Sperm and Relation to Capacitation and Zona Pellucida Binding Biol Reprod, April 1, 2003; 68(4): 1463 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ficarro, O. Chertihin, V. A. Westbrook, F. White, F. Jayes, P. Kalab, J. A. Marto, J. Shabanowitz, J. C. Herr, D. F. Hunt, et al. Phosphoproteome Analysis of Capacitated Human Sperm. EVIDENCE OF TYROSINE PHOSPHORYLATION OF A KINASE-ANCHORING PROTEIN 3 AND VALOSIN-CONTAINING PROTEIN/p97 DURING CAPACITATION J. Biol. Chem., March 21, 2003; 278(13): 11579 - 11589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tardif, C. Dube, and J. L. Bailey Porcine Sperm Capacitation and Tyrosine Kinase Activity Are Dependent on Bicarbonate and Calcium but Protein Tyrosine Phosphorylation Is Only Associated with Calcium Biol Reprod, January 1, 2003; 68(1): 207 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Schuffner, H. S. Bastiaan, H. E. Duran, Z.-Y. Lin, M. Morshedi, D. R. Franken, and S. Oehninger Zona pellucida-induced acrosome reaction in human sperm: dependency on activation of pertussis toxin-sensitive Gi protein and extracellular calcium, and priming effect of progesterone and follicular fluid Mol. Hum. Reprod., August 1, 2002; 8(8): 722 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Allegrucci, L. Liguori, and A. Minelli Stimulation by N6-Cyclopentyladenosine of A1 Adenosine Receptors, Coupled to G{{alpha}}i2 Protein Subunit, Has a Capacitative Effect on Human Spermatozoa Biol Reprod, June 1, 2001; 64(6): 1653 - 1659. [Abstract] [Full Text]
|
|
|
|
|
|
K.D. Nusser, S. Mitalipov, A. Widmann, B. Gerami-Naini, R.R. Yeoman, and D.P. Wolf Developmental competence of oocytes after ICSI in the rhesus monkey Hum. Reprod., January 1, 2001; 16(1): 130 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Cross Sphingomyelin Modulates Capacitation of Human Sperm In Vitro Biol Reprod, October 1, 2000; 63(4): 1129 - 1134. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. T. S. Agustin, C. G. Wilkerson, and G. B. Witman The Unique Catalytic Subunit of Sperm cAMP-dependent Protein Kinase Is the Product of an Alternative Calpha mRNA Expressed Specifically in Spermatogenic Cells Mol. Biol. Cell, September 1, 2000; 11(9): 3031 - 3044. [Abstract] [Full Text]
|
|
|
|
|
|
C. Wu, T. Stojanov, O. Chami, S. Ishii, T. Shimuzu, A. Li, and C. O'Neill Evidence for the Autocrine Induction of Capacitation of Mammalian Spermatozoa J. Biol. Chem., July 13, 2001; 276(29): 26962 - 26968. [Abstract] [Full Text] [PDF]
|
|