Presenilins Interact with Rab11, a Small GTPase Involved in the Regulation of Vesicular Transport

• Published in: Human molecular genetics 1999-07, Vol.8 (7), p.1263-1269
• Main Authors: Dumanchin, Cécile, Czech, Christian, Campion, Dominique, Cuif, Marie Hélène, Poyot, Thomas, Martin, Cosette, Charbonnier, Françoise, Goud, Bruno, Pradier, Laurent, Frebourg, Thierry
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Biological and medical sciences; Biological Transport - physiology; Cell physiology; COS Cells; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; GTP Phosphohydrolases - metabolism; GTP-Binding Proteins - metabolism; Humans; Medical sciences; Membrane and intracellular transports; Membrane Proteins - metabolism; Molecular and cellular biology; Molecular Sequence Data; Neurology; Presenilin-1; Protein Conformation; rab GTP-Binding Proteins; Saccharomyces cerevisiae - metabolism
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/8.7.1263

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 interaction suggests that PSs might be involved in amyloid precursor protein vesicular routing.