INVESTIGADORES
SUHAIMAN Laila
congresos y reuniones científicas
Título:
PIP2 promotes membrane curvature and is a signaling hub in human sperm acrosome exocytosis
Autor/es:
ALTAMIRANO, KARINA N; SUHAIMAN, LAILA; LUCCHESI, O; RUETE, CELESTE; BELMONTE, SILVIA A
Lugar:
Parana, Entre Ríos
Reunión:
Congreso; 54th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2018
Institución organizadora:
SAIB
Resumen:
The humansperm has a secretory vesicle that undergoes exocytosis when challenged withdifferent stimuli; known as acrosomal reaction (AR); and requires the fusion ofthe outer acrosome membrane and plasma membrane. We reported that DAGstimulates AR by feeding into a PKC and PLD1-dependentpositive loop that supplies PIP2. We hypothesize that PIP2synthesis is required to produce DAG and IP3, and to induce a changein the acrosomal membrane curvature. We resort to Molecular Dynamicssimulations and TEM experiments to demonstrate that PIP2 increaseinduces the formation of deep acrosomal membrane invaginations; although it wasnot able to induce acrosome swelling; AR; nor membrane disruption. However, forthe AR to proceed, PIP2 needs to be hydrolyzed. Previous work led usto propose the following signaling pathway: cAMP-Epac-Rap1-PLCε.The hydrolysis of PIP2 generates IP3, which binds IP3-sensitivechannels and releases Ca2+ from the acrosome. We demonstrate thepresence of a nucleotide exchange factor activated by DAG (RasGRP1), describedto activate Rap1 in secretory cells, by WB and IFI. Also, we proved RasGRP1ability to trigger AR in a dose-dependent manner. Furthermore, as shown by Far-IFI,DAG was able to activate Rap1 indicating that is involved in the pathwaydescribed previously. Our findings remark the dual role of PIP2 inexocytosis and report a direct evidence of the presence and function of RasGRP1in the signaling module cAMP-Epac-Rap1-PLCε in AR.