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J Lipid Res. 2011 Aug;52(8):1471-82. doi: 10.1194/jlr.M013284. Epub 2011 May 17.

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

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  • 1Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

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.

PMID:
21586796
[PubMed - indexed for MEDLINE]
PMCID:
PMC3139239
Free PMC Article
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