Rab6 interacts with the mint3 adaptor protein.
The Rab6 GTPase regulates a retrograde transport route connecting endosomes and the endoplasmic reticulum (ER) via the Golgi apparatus. Recently it was shown that active (GTP-loaded) Rab6A regulates intracellular processing of the amyloid precursor protein (APP). To characterize the role of Rab6A in APP trafficking and to identify effector proteins of the active Rab6A protein, we screened a human placenta cDNA library using the yeast two-hybrid system. We isolated an interacting cDNA clone encoding part of the adaptor protein mint3. The interaction between Rab6A and mint3 is GTP-dependent and requires the complete phosphotyrosine-binding (PTB) domain of the mint protein, which also mediates the association with APP. By confocal microscopy we show that Rab6A, mint3 and APP co-localize at Golgi membranes in HeLa cells. Density gradient centrifugation of cytosolic extracts confirms a common distribution of these three proteins. Our data suggest that mint3 links Rab6A to APP traffic.
Teber
Iskender
I
Department of Experimental Tumor Biology, University of Münster, D-48149 Germany.
Nagano
Fumiko
F
Kremerskothen
Joachim
J
Bilbilis
Konstantinos
K
Goud
Bruno
B
Barnekow
Angelika
A
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D010957:Plasmids; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
C117536:APBA3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D011506:Proteins; C094135:Rab6 protein; D020691:rab GTP-Binding Proteins