• PMID: 29700114
• Gene Name: CATSPER1
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

Disruption of protein kinase A localization induces acrosomal exocytosis in capacitated mouse sperm

Stival C, Ritagliati C, Xu X, Gervasi MG, Luque GM, Baró Graf C, De la Vega-Beltrán JL, Torres N, Darszon A, Krapf D, Buffone MG, Visconti PE, Krapf D.

Protein kinase A (PKA) is a broad-spectrum Ser/Thr kinase involved in the regulation of several cellular activities. Thus, its precise activation relies on being localized at specific subcellular places known as discrete PKA signalosomes. A-Kinase anchoring proteins (AKAPs) form scaffolding assemblies that play a pivotal role in PKA regulation by restricting its activity to specific microdomains. Because one of the first signaling events observed during mammalian sperm capacitation is PKA activation, understanding how PKA activity is restricted in space and time is crucial to decipher the critical steps of sperm capacitation. Here, we demonstrate that the anchoring of PKA to AKAP is not only necessary but also actively regulated during sperm capacitation. However, we find that once capacitated, the release of PKA from AKAP promotes a sudden Ca(2+) influx through the sperm-specific Ca(2+) channel CatSper, starting a tail-to-head Ca(2+) propagation that triggers the acrosome reaction. Three-dimensional super-resolution imaging confirmed a redistribution of PKA within the flagellar structure throughout the capacitation process, which depends on anchoring to AKAP. These results represent a new signaling event that involves CatSper Ca(2+) channels in the acrosome reaction, sensitive to PKA stimulation upon release from AKAP. CI - © 2018 Stival et al. FAU - Stival, Cintia AU - Stival C AD - From the Laboratoty of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario 2000, Argentina. FAU - Ritagliati, Carla AU - Ritagliati C AD - From the Laboratoty of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario 2000, Argentina. FAU - Xu, Xinran AU - Xu X AD - the Department of Electrical and Computer Engineering, Colorado State University, Fort Collins, Colorado 80523. FAU - Gervasi, Maria G AU - Gervasi MG AD - the Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003. FAU - Luque, Guillermina M AU - Luque GM AD - the Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires C1428ADN, Argentina. FAU - Baró Graf, Carolina AU - Baró Graf C AD - From the Laboratoty of Cell Signal Transduction Networks, Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET-UNR, Rosario 2000, Argentina. FAU - De la Vega-Beltrán, José Luis AU - De la Vega-Beltrán JL AD - the Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología (IBT), Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos 62210, México, and. FAU - Torres, Nicolas AU - Torres N AD - the Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires C1428ADN, Argentina. FAU - Darszon, Alberto AU - Darszon A AD - the Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología (IBT), Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos 62210, México, and. FAU - Krapf, Diego AU - Krapf D AD - the Department of Electrical and Computer Engineering, Colorado State University, Fort Collins, Colorado 80523. AD - the School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523. FAU - Buffone, Mariano G AU - Buffone MG AD - the Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires C1428ADN, Argentina. FAU - Visconti, Pablo E AU - Visconti PE AD - the Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003.