Transient abundance of presenilin 1 fragments/nicastrin complex associated with synaptogenesis during development in rat cerebellum

Immunolocalization and expression of endogenous nicastrin (NCT) and presenilin 1 (PS1) fragments during postnatal development of rat cerebellum were investigated with fragment-specific antibodies. Immunoblotting for NCT revealed the expected mature and immature species, which gradually declined during development. In contrast, the expression of PS1 N-terminal fragment exhibited a peak at postnatal day 14 (P14) and declined thereafter. This chronological change was similarly observed with PS1 C-terminal fragment. Immunoprecipitation of NCT indicated its physical association with PS1 fragments. Colocalization of these molecules to the endoplasmic reticulum in cerebellar Purkinje cells indicates that they are organized into a complex in developing neurons. In addition, active sites of synaptogenesis, the base of the external granular layer and glomeruli, contained PS1 fragments and smaller amount of NCT. Isolated synaptic fraction contained both PS1 and NCT, suggesting their functional association within synapses. Transient abundance of NCT and PS1 fragments as a complex, when (P14) and where synaptogenesis is active, is consistent with intracellular trafficking of this complex in developing neurons and suggests its role as γ-secretase in synaptogenesis.