PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein.
In epithelial cells, sorting of membrane proteins to the basolateral surface depends on the presence of a basolateral sorting signal (BaSS) in their cytoplasmic domain. Amyloid precursor protein (APP), a basolateral protein implicated in the pathogenesis of Alzheimer's disease, contains a tyrosine-based BaSS, and mutation of the tyrosine residue results in nonpolarized transport of APP. Here we report identification of a protein, termed PAT1 (protein interacting with APP tail 1), that interacts with the APP-BaSS but binds poorly when the critical tyrosine is mutated and does not bind the tyrosine-based endocytic signal of APP. PAT1 shows homology to kinesin light chain, which is a component of the plus-end directed microtubule-based motor involved in transporting membrane proteins to the basolateral surface. PAT1, a cytoplasmic protein, associates with membranes, cofractionates with APP-containing vesicles, and binds microtubules in a nucleotide-sensitive manner. Cotransfection of PAT1 with a reporter protein shows that PAT1 is functionally linked with intracellular transport of APP. We propose that PAT1 is involved in the translocation of APP along microtubules toward the cell surface.
Zheng
P
P
Institute of Pathology and Cell Biology Program, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943, USA.
Eastman
J
J
Vande Pol
S
S
Pimplikar
S W
SW
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017421:Sequence Analysis; D015398:Signal Transduction
D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; C103266:PAT1 protein, S cerevisiae; D011506:Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins