Details

Autor(en) / Beteiligte

• Suga, Kei
• Saito, Ayako
• Tomiyama, Takami
• Mori, Hiroshi
• Akagawa, Kimio

Titel

Syntaxin 5 interacts specifically with presenilin holoproteins and affects processing of βAPP in neuronal cells

Ist Teil von

• Journal of neurochemistry, 2005-07, Vol.94 (2), p.425-439

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The specific roles of syntaxin 5 (Syx 5) in the interaction with presenilin (PS) and the accumulation of β‐amyloid precursor protein (βAPP), as well as the secretion of β‐amyloid peptide (Aβ peptide) were examined in NG108‐15 cells. Syx 5, which localizes from the endoplasmic reticulum (ER) to the Golgi, bound to PS holoproteins, while the other Syxs studied did not. Among familial Alzheimer's disease (FAD)‐linked PS mutants, PS1ΔE9, which lacks the endoproteolytic cleavage site, showed markedly decreased binding to Syx 5. The interaction domains in Syx 5 were mapped to the transmembrane region and to the cytoplasmic region containing the α‐helical domains, which are distinct from the H3 (SNARE motif). Among all of the Syxs examined, only overexpression of Syx 5 resulted in the accumulation of βAPP in the ER to cis‐Golgi compartment, an attenuation of the amount of the C‐terminal fragment (APP‐CTF) of βAPP, and a reduction in the secretion of Aβ peptides. Furthermore, co‐expression of Syx 5 with C99 resulted in an increase in APP‐CTF and suppressed Aβ secretion. Taken together, these results indicate that Syx 5 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 of neuronal cells.