Identification of syntaxin 1A as a novel binding protein for presenilin-1

γ-Secretase and Presenilin Mediate Cleavage and Phosphorylation of Vascular Endothelial Growth Factor Receptor-1

“…Some consensus exists that the mechanism involves the association between Fl.PS and transport proteins (32, 33). Indeed, a recent detailed study of PS interacting with β-catenin indicates that a GSK3β-induced structural change of the hydrophilic loop of Fl.PS1 leads to decreased phosphorylation and ubiquitination of β-catenin (34).…”

The very many faces of presenilins and the γ-secretase complex

“…A protein-protein interaction study (Dumanchin et al 1999) showed that human PS1 and PS2 interact with Rab11 — a small GTPase known to be a master regulator of protein transport via recycling endosomes (Jing and Prekeris 2009). Similarly, syntaxin 5 and syntaxin 1A, two SNAREs involved in Golgi trafficking and synaptic vesicle fusion, respectively, also bind to PS (Smith et al 2000; Suga et al 2005). In addition, localization of active γ-secretase complexes in synaptic vesicles has been demonstrated (Frykman et al 2010).…”

Presenilin-dependent regulated intramembrane proteolysis and γ-secretase activity

“…Loop domain GTPase; regulation of vesicular transport [201] RabGDI N-terminus Rab GDP dissociation inhibitor [202] RYR2 C-terminus Cardiac ryanodine receptor; calcium signalling [104] RyR N-terminus Mouse brain ryanodine receptor; calcium signalling [105] Sorcin Loop domain Regulator of ryanodine receptor [106] Sel-10 E3 ubiquitin ligase [108] Syntaxin 1A Loop domain Synaptic plasma membrane protein [203] Syntaxin 5 Full length ER-Golgi vesicular transport [204] tau N-Terminus Microtubule-binding protein [101] Telencephalin C-terminus Neuron-specific adhesion molecule [205] TRAF6 IL-1R1 and NGFR signalling [133,206] TMP21 Protein transport [61] TPIP N-terminus Tetratricopeptide repeat-containing protein [207] Ubiquilin C-terminus Ubiquitin domain-containing protein [208] X11a & X11b C-terminus Neuronal adapter proteins [209] the p75 NTR and syndecan-3, suggest that presenilindependent regulated intramembrane proteolysis may also function in non-nuclear signalling events such as regulating formation/disassembly of cell-surface heteromeric receptor complexes [139], while g-secretase cleavage of E-cadherin contributes to adherens junction disassembly, whereas others are inherently labile species, produced as a by-product of proteolysis and receptor degradation [11]. Despite the preliminary and inconclusive nature of some studies and the apparent diversity of g-secretase substrates, from comparative biochemical and genetic studies it is becoming apparent that regulated intramembrane proteolysis is critically involved in the regulation of several pathways of signal transduction and essential for embryonic development, tissue homeostasis, defects which contribute to the onset of disease [1,2,132,140].…”