The small GTPase Rab6 interacts with Mint1
Abstract
Alzheimer's Disease (AD) is the most prevalent neuronal degenerative disorder worldwide. Patients suffering from it show amyloidogenic plaques, which consist of abeta, a proteolytic cleavage product deriving from the processing of the amyloid precursor protein (APP). The cleavage of APP seems to be modulated by a number of regulators, one group of them being the Mint adaptor proteins [1]. We have previously shown that the ubiquitously expressed Mint3 interacts with the small GTPase Rab6, which is known to play a key role in Golgi associated vesicle trafficking processes [2,3,4]. Prior studies indicated an involvement of Rab6 in the processing of APP, which makes the connection between Rab6, APP and the Mint adaptor proteins an interesting field of research in the development of AD [5]. Here we report, that the neuronal protein Mint1 interacts with the constitutively active variant of Rab6 in vivo. Further experiments also proved that the PTB domain of Mint1 is the area to interact with this small GTPase.
References
[1] Borg, J. P., Ooi, J., Levy, E. and Margolis, B. (1996). The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol. Cell Biol. 16, 6229-6241.
[2] Teber, I., Nagano, F., Kremerskothen, J., Bilbilis, K., Goud, B. and Barnekow, A. (2005). Rab6 interacts with the mint3 adaptor protein. Biol. Chem. 386, 671-677.
[3] Martinez, O., Schmidt, A., Salamero, J., Hoflack, B., Roa, M. and Goud, B. (1994). The small GTP-binding protein rab6 functions in intra-Golgi transport. J.Cell Biol. 127, 1575-1588.
[4] Barnekow, A., Thyrock, A. and Kessler, D. (2009). Rab proteins and their interaction partners. Int. Rev. Cell Mol. Biol. 274, 235-274.
[5] Scheper, W., Zwart, R. and Baas, F. (2004). Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events. Brain Res. Mol. Brain Res. 122, 17-23.
