Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
| Autor: | Lis C, Puga Molina, Nicolás A, Pinto, Paulina, Torres Rodríguez, Ana, Romarowski, Alberto, Vicens Sanchez, Pablo E, Visconti, Alberto, Darszon, Claudia L, Treviño, Mariano G, Buffone |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
CIENCIAS MÉDICAS Y DE LA SALUD
Intracellular Space Inmunología Cystic Fibrosis Transmembrane Conductance Regulator Alkalies Benzoates Models Biological Article Membrane Potentials purl.org/becyt/ford/1 [https] Ciencias Biológicas Chlorides Cell Movement Cyclic AMP Humans Phosphorylation CFTR purl.org/becyt/ford/1.6 [https] Protein Kinase Inhibitors CYCLIC AMP Sulfonamides Acrosome Reaction HUMANS purl.org/becyt/ford/3.1 [https] SPERM CAPACITATION respiratory system Hydrogen-Ion Concentration Isoquinolines Cyclic AMP-Dependent Protein Kinases Medicina Básica ALKALINIZATION Thiazolidines purl.org/becyt/ford/3 [https] Biología Reproductiva Sperm Capacitation CIENCIAS NATURALES Y EXACTAS Signal Transduction |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| DOI: | 10.1002/jcp.25634 |
| Popis: | 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. Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; México Fil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; México Fil: Visconti, Pablo E.. University of Massachussets; Estados Unidos Fil: Darszon, Alberto. Universidad Nacional Autónoma de México; México Fil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; México Fil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|