A missense mutation in the membrane trafficking protein αSNAP impairs fertility in female mice

CAPPA, ANDREA ISABEL; MICHAUT, MARCELA ALEJANDRA; DE PAOLA, MARIA MATILDE; GARRIDO, FACUNDO ; ARCOS, ALEXIS; BATIZ, LUIS FEDERICO

La Serena

Workshop; EMBO Workshop: ?Actualizations in Membrane Trafficking in Health and Disease Current Advances in Membrane Trafficking: implications for cell polarity?.; 2016

EMBO. European Molecular Biology Organization

αSNAP is a ubiquitous and essential component of membrane fusion machinerywhich plays a key role in different aspects of cell biology such as vesicular traffic andexocytosis, and many others like cell polarity, cell division, regulation of ephitelialjunctions and apoptosis. Deletion of αSNAP is embryonically lethal, however thespontaneous mutant hyh mice, carrying a missense mutation in Napa gene (M105I),serve as a unique model to study αSNAP function in vivo. We have determined thathyh female have a strongly reduced fertility. Hyh female mice had a significantlydecreased ovulation and in vitro fertilization rates compared with wild-type mice.Previously we have determined that αSNAP is required for cortical granulesexocytosis (CGE), the primary mechanism in preventing polyspermic fertilization. Anincreased rate of polyspermy in in vitro fertilization assays was observed in hyh mice,suggesting that M105I mutation impairs CGE. In order to test this hipothesis we nextperformed different CGE assays after in vitro fertilization and partenogenetic activation,which showed that hyh oocytes exhibit a diminished CGE. Interestingly, some hyh MIIoocytes showed an abnormal CG pattern, suggesting that αSNAP might have afunction in the polarity establishment during oocyte maturation. Furthermore, hyhoocytes presented an altered subcellular αSNAP localization compared with wild typeoocytes, as well as an atypical distribution of mitochondrial and Golgi markers.Moreover, cumulus-oocyte complex from hyh female showed a significantly increasedof apoptosis, that correlates with a pronounced decreased in αSNAP and N-Cadherinexpression in cumulus cells. These results suggest that αSNAP has an important rolein the maintenance of N-cadherin-based junctions and survival of cumulus cells.Together, our findings revealed that M105I mutation in αSNAP leads to multifactorialfertility defects in hyh female mice, demonstrating that αSNAP plays an important rolein female reproduction.