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

作者：Beers Michael F; Hawkins Arie; Shuman Henry; Zhao Ming; Newitt Jennifer L; Maguire Jean Ann; Ding Wenge; Mulugeta Surafel^*

来源：The Journal of Lipid Research, 2011, 52(8): 1471-1482.

DOI：10.1194/jlr.M013284

• ATP binding cassette, class A
• ABCA3
• protein trafficking
• post-Golgi sorting

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.-Beers, M. F., A. Hawkins, H. Shuman, M. Zhao, J. L. Newitt, J. A. Maguire, W. Ding, and S. Mulugeta. A novel conserved targeting motif found in ABCA transporters mediates trafficking to early post-Golgi compartments. J. Lipid Res. 2011. 52: 1471-1482.

• 出版日期2011-8