Abstract
We have previously shown that presenilin 1 and 2 (PS1 and PS2) bind to syntaxin 5 (Syx5). In this study, we examined the interaction of PSs with Syx isoforms, the effects of Syx overexpression on β-amyloid precursor protein (βAPP), and the Aβ peptide production in NG108-15 cells. The data showed that Syx5 which localizes from the endoplasmic reticulum to the Golgi binds to PS holoproteins, while other Syxs, so far studied did not. Among familial Alzheimer's disease (FAD)-linked PS mutants, PS1deltaE9, which lacks the region containing the endoproteolytic cleavage site, showed markedly decreased binding to Syx5. The interaction domains in Syx5 were mapped to the transmembrane region and to the cytoplasmic region containing the α-helical domains, which are distinct from the H3 (SNARE motif). Furthermore, among the Syxs examined, the overexpression of Syx5 resulted in the accumulation of βAPP and reduced the secretion of Aβ peptides (Aβ40 and Aβ42) in NG108-15 cells. Taken together, these results indicate that Syx5 may play a specific role in the modulation of processing and/or trafficking of FAD-related proteins in neuronal cells by interaction with PS holoproteins in the early secretory compartment. [Jpn J Physiol 55 Suppl:S83 (2005)]
