Cellular localization and trafficking of the human ABCA1 transporter.

Abstract

ABCA1, the ATP-binding cassette protein mutated in Tangier disease, mediates the efflux of excess cellular sterol to apoA-I and thereby the formation of high density lipoprotein. The intracellular localization and trafficking of ABCA1 was examined in stably and transiently transfected HeLa cells expressing a functional human ABCA1-green fluorescent protein (GFP) fusion protein. The fluorescent chimeric ABCA1 transporter was found to reside on the cell surface and on intracellular vesicles that include a novel subset of early endosomes, as well as late endosomes and lysosomes. Studies of the localization and trafficking of ABCA1-GFP in the presence of brefeldin A or monensin, agents known to block intracellular vesicular trafficking, as well as apoA-I-mediated cellular lipid efflux, showed that: (i) ABCA1 functions in lipid efflux at the cell surface, and (ii) delivery of ABCA1 to lysosomes for degradation may serve as a mechanism to modulate its surface expression. Time-lapse fluorescence microscopy revealed that ABCA1-GFP-containing early endosomes undergo fusion, fission, and tubulation and transiently interact with one another, late endocytic vesicles, and the cell surface. These studies establish a complex intracellular trafficking pathway for human ABCA1 that may play important roles in modulating ABCA1 transporter activity and cellular cholesterol homeostasis.

• Authors: E B Neufeld, A T Remaley, S J Demosky, J A Stonik, A M Cooney, M Comly, N K Dwyer, M Zhang, J Blanchette-Mackie, S Santamarina-Fojo, H B Brewer Jr
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 29 Pg. 27584-90 (Jul 20 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11349133 (Publication Type: Journal Article)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters
• Apolipoprotein A-I
• Luminescent Proteins
• Recombinant Fusion Proteins
• Sterols
• Green Fluorescent Proteins
• Monensin
• Cycloheximide

Topics

• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Apolipoprotein A-I (metabolism)
• Biological Transport
• CHO Cells
• Cell Compartmentation
• Cricetinae
• Cycloheximide (pharmacology)
• Endocytosis
• Green Fluorescent Proteins
• HeLa Cells
• Humans
• Immunohistochemistry
• Luminescent Proteins (genetics)
• Monensin (pharmacology)
• Recombinant Fusion Proteins (genetics)
• Sterols (metabolism)
• Transfection