title: Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport.
abstract: Presenilin 1 (PS1) mutations account for the majority of early-onset dominant cases of familial Alzheimer's disease. Presenilins (PSs) are located in many intra-cellular compartments such as the endoplasmic reticulum, Golgi apparatus, nuclear region and vesicular structures. These proteins include from seven to nine putative transmembrane domains, with the N- and C-terminal ends and a large hydrophilic loop orientated towards the cytoplasm. We report an interaction between the human PS1 or PS2 hydrophilic loop and Rab11, a small GTPase belonging to the Ras-related superfamily. Interaction domains were mapped to codons 374-400 for PS1 and to codons 106-179 for Rab11, a region including the fourth GTP-binding domain. Considering the implication of Rab proteins in vesicular transport pathways, the PS-Rab11 inter-action suggests that PSs might be involved in amyloid precursor protein vesicular routing.
authors.affiliation: INSERM EPI 9906, Faculté de Médecine et de Pharmacie, 22 Boulevard de Gambetta, 76183 Rouen and IFRMP, Mont-Saint-Aignan, 76821 Rouen Cedex, France,
authors.forename: C
authors.initials: C
authors.lastname: Dumanchin
authors.forename: C
authors.initials: C
authors.lastname: Czech
authors.forename: D
authors.initials: D
authors.lastname: Campion
authors.forename: M H
authors.initials: MH
authors.lastname: Cuif
authors.forename: T
authors.initials: T
authors.lastname: Poyot
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Charbonnier
authors.forename: B
authors.initials: B
authors.lastname: Goud
authors.forename: L
authors.initials: L
authors.lastname: Pradier
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D053764:Presenilin-1; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
chemical_list: D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D008565:Membrane Proteins; D053764:Presenilin-1; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C508853:PSEN1 protein, human