Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport.
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.
Dumanchin
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C
INSERM EPI 9906, Faculté de Médecine et de Pharmacie, 22 Boulevard de Gambetta, 76183 Rouen and IFRMP, Mont-Saint-Aignan, 76821 Rouen Cedex, France,
Czech
C
C
Campion
D
D
Cuif
M H
MH
Poyot
T
T
Martin
C
C
Charbonnier
F
F
Goud
B
B
Pradier
L
L
Frebourg
T
T
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
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