IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A highly organized signaling distribution complex is critical for the development of mammalian sperm hyperactivation
Autor/es:
ROMAROWSKI A; UGO B; BUFFONE MG; D ́ALOTTO T; GILIO N; LUQUE GM; PUGA MOLINA LC; KRAPF D
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión científica de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Sperm acquire the ability to fertilize in the female genital tract in a process called capacitation. From a molecular point of view, bicarbonate and Calcium (Ca2+) stimlation of the soluble adenylyl cyclase leads to the activation of the cAMP/PKA pathway. During capacitation sperm undergo a change in the motility pattern called hyperactivation (HA) which is critical to fertilization. Ca2+ is the primary second messenger that triggers this motility and it depends on CatSper channels. It has been described that CatSper1 proteins form a unique pattern of four linear ??stripes?? running down the principal piece of the flagellum. Catsper Ca2+ domains orchestrate the timing and extent of complex phosphorylation cascades because it colocalizes with Ca2+ signaling molecules. Our central hypothesis is that Cdc42 is an essential component of the highly organized signaling complex that controls intracellular Ca2+ through CatSper channels during mammalian sperm capacitation. This spatial distribution is critical for the development of HA. Using super-resolution microscopy, we observed that Cdc42 localized in the sperm tail and form a pattern of four linear ??stripes?? running down the principal piece, which resembles the localization of CatSper. By using a specific inhibitor of Cdc42, we detected that PKA-dependent phosphorylation were completely abrogated. This inhibition was bypassed by using membrane permeable analogs of cAMP. The rise in intracellular Ca2+ that occurs during capacitation as a result of CatSper activation, was abrogated with Cdc42 inhibition. When sperm where incubated in the presence of Cdc42 inhibitors, we observed a strong decrease in percentage of HA. This is consistent with the low levels of intracellular Ca2+ observed. All together, these results suggest that Cdc42 is participating in a molecular complex with CatSper channels modulating the levels of intracellular Ca2+ and ultimately, the development of HA.