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PMID: 27714810 Published · ppublish English Journal Article

Essential Role of CFTR in PKA-Dependent Phosphorylation, Alkalinization, and Hyperpolarization During Human Sperm Capacitation.

Journal of cellular physiology ·Vol. 232 ·No. 6 ·2017-06-00 ·Pages 1404-1414

Puga Molina LC, Pinto NA, Torres Rodríguez P, Romarowski A, Vicens Sanchez A, Visconti PE, Darszon A, Treviño CL, Buffone MG

Abstract

Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3- is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3- is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3- -entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation. J. Cell. Physiol. 232: 1404-1414, 2017. © 2016 Wiley Periodicals, Inc.

MeSH Terms
Acrosome Reaction/drug effects Alkalies/metabolism Benzoates/metabolism Cell Movement/drug effects Chlorides/metabolism Cyclic AMP/agonists,metabolism Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,metabolism Cystic Fibrosis Transmembrane Conductance Regulator/metabolism Humans Hydrogen-Ion Concentration Intracellular Space/drug effects,metabolism Isoquinolines/pharmacology Membrane Potentials/drug effects Models, Biological Phosphorylation/drug effects Protein Kinase Inhibitors/pharmacology Signal Transduction/drug effects Sperm Capacitation/drug effects Sulfonamides/pharmacology Thiazolidines/metabolism
Chemicals
3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone Alkalies Benzoates Chlorides Isoquinolines Protein Kinase Inhibitors Sulfonamides Thiazolidines Cystic Fibrosis Transmembrane Conductance Regulator Cyclic AMP Cyclic AMP-Dependent Protein Kinases N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Puga Molina Lis C
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
Pinto Nicolás A
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
Torres Rodríguez Paulina
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México.
Romarowski Ana
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
Vicens Sanchez Alberto
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México.
Visconti Pablo E
Department of Veterinary and Animal Science, Paige Labs, University of Massachusetts, Amherst, Massachusetts.
Darszon Alberto
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México.
Treviño Claudia L
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México.
Buffone Mariano G
Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
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Article Info
Journal
Journal of cellular physiology
Abbr.
J Cell Physiol
ISSN
1097-4652
DOI
10.1002/jcp.25634
Published
2017-06-00
Epub
2016-00-26
Pages
1404-1414
Language
English
Region
United States
NLM ID
0050222
PMCID
PMC5548537
Subset
IM
Grants
NICHD NIH HHS · R01 HD038082 · United States
NICHD NIH HHS · R01 HD044044 · United States
External Links
PubMed source DOI: 10.1002/jcp.25634 PMC Full Text View journal details
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