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Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
Author(s) -
Navarrete Felipe A.,
GarcíaVázquez Francisco A.,
Alvau Antonio,
Escoffier Jessica,
Krapf Dario,
SánchezCárdenas Claudia,
Salicioni Ana M.,
Darszon Alberto,
Visconti Pablo E.
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24873
Subject(s) - capacitation , tyrosine phosphorylation , phosphorylation , egta , sperm , microbiology and biotechnology , calmodulin , signal transduction , biology , protein tyrosine phosphatase , tyrosine , calcium , chemistry , biochemistry , enzyme , botany , organic chemistry
Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up‐regulation of a cAMP‐dependent pathway, changes in intracellular pH, intracellular Ca 2+ , and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca 2+ ions have a biphasic role in the regulation of cAMP‐dependent signaling. Media without added Ca 2+ salts (nominal zero Ca 2+ ) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca 2+ . However, chelation of the extracellular Ca 2+ traces by EGTA induced both cAMP‐dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca 2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca 2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild‐type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca 2+ media. Therefore, sperm lacking Catsper Ca 2+ channels behave as wild‐type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca 2+ involved in the regulation of cAMP‐dependent and tyrosine phosphorylation pathways required for sperm capacitation. J. Cell. Physiol. 230: 1758–1769, 2015. © 2015 Wiley Periodicals, Inc.