A novel conserved targeting motif found in ABCA transporters mediates trafficking to early post-Golgi compartments[S]

• Main Authors: Michael F. Beers, Arie Hawkins, Henry Shuman, Ming Zhao, Jennifer L. Newitt, Jean Ann Maguire, Wenge Ding, Surafel Mulugeta
• Format: Article
• Language: English
• Published: Elsevier 2011-08-01
• Series: Journal of Lipid Research
• Subjects: ATP binding cassette, class A; ABCA3; protein trafficking; post-Golgi sorting
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520369224

The ATP binding cassette, class A (ABCA) proteins are homologous polytopic transmembrane transporters that function as lipid pumps at distinct subcellular sites in a variety of cells. Located within the N terminus of these transporters, there exists a highly conserved xLxxKN motif of unknown function. To define its role, human ABCA3 was employed as a primary model representing ABCA transporters, while mouse ABCA1 was utilized to support major findings. Transfection studies showed colocalization of both transporters with surfactant protein C (SP-C), a marker peptide for successful protein targeting to lysosomal-like organelles. In contrast, alanine mutation of xLxxKN resulted in endoplasmic reticulum retention. As proof of principle, swapping xLxxKN for the known lysosomal targeting motif of SP-C resulted in post-Golgi targeting of the SP-C chimera. However, these products failed to reach their terminal processing compartments, suggesting that the xLxxKN motif only serves as a Golgi exit signal. We propose a model whereby an N-terminal signal sequence, xLxxKN, directs ABCA transporters to a post-Golgi vesicular sorting station where additional signals may be required for selective delivery of individual transporters to final subcellular destinations.