title: The Syntaxin 5 isoforms Syx5 and Syx5L have distinct effects on the processing of {beta}-amyloid precursor protein.
abstract: In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of beta-amyloid precursor protein (betaAPP). Similar to Syx5, Syx5L bound to PS1 holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular betaAPP holoprotein, and did not inhibit amyloid beta peptide (Abeta) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of betaAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular betaAPP holoprotein and reduction in the secretion of Abeta. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of betaAPP in the early secretory compartment.
authors.affiliation: Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan. ksuga@ks.kyorin-u.ac.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Suga
authors.forename: Ayako
authors.initials: A
authors.lastname: Saito
authors.forename: Takami
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Kimio
authors.initials: K
authors.lastname: Akagawa
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D053763:Presenilins / Q000378:metabolism*; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D053763:Presenilins; D020033:Protein Isoforms; D050765:Qa-SNARE Proteins