Molecular and Functional Interaction of the ATP-binding Cassette Transporter A1 with Fas-associated Death Domain Protein

Buechler, Christa; Bared, Salim Maa; Aslanidis, Charalampos; Ritter, Mirko; Drobnik, Wolfgang; Schmitz, Gerd

doi:10.1074/jbc.c200436200

Cited by 25 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results suggest that apoA-I activates cAMP signaling through an ABCA1 transporter coupled to the G s protein. This concept of ABCA1-mediated signaling was supported by the identification of a functional association between ABCA1 and the fas-associated death domain protein, an adaptor molecule mainly described in death receptor signal transduction (28). Furthermore, Cdc42 was reported to interact directly with ABCA1, and this interaction was suggested to influence intracellular lipid trafficking and apoA-I-mediated cholesterol efflux (29,30).…”

Section: Discussionmentioning

confidence: 94%

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

Haidar

Denis

Marcil

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

It has been suggested that the signal transduction pathway initiated by apoA-I activates key proteins involved in cellular lipid efflux. We investigated apoA-Imediated cAMP signaling in cultured human fibroblasts induced with (22R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Treatment of stimulated fibroblasts with apoA-I for short periods of time (<45 min) increased ATP binding cassette A1 (ABCA1) phosphorylation in a concentration-dependent manner. Concomitantly, apoA-I increased the intracellular level of cAMP in a concentration-and time-dependent manner. The maximal cAMP level was reached within 10 min at 10 g/ml apoA-I representing a 1-fold increase. The ability of apoA-I to mediate cAMP production was only observed in stimulated fibroblasts. Furthermore, overexpression of ABCA1 in Chinese hamster ovary cells resulted in a 1.5-fold increase in apoA-I-mediated cAMP accumulation as compared with untransfected cells. In contrast, forskolin increased cAMP production significantly in unstimulated fibroblasts as well as in untransfected Chinese hamster ovary cells. Pharmacological inhibition of protein kinase A (H89) completely blocked apoA-I-mediated ABCA1 phosphorylation. Naturally occurring mutations of ABCA1 associated with Tangier disease (C1477R, 2203X, and 2145X) severely reduced apoA-I-mediated cAMP production, ABCA1 phosphorylation, 125 I-apoA-I binding, and lipid efflux, without affecting forskolin-mediated cAMP elevation. In contrast, the protein kinase A catalytic subunit was able to phosphorylate ABCA1 similarly from mutant and normal cell lines in vitro. Together, our results indicate that apoA-I activates ABCA1 phosphorylation through the cAMP/ protein kinase A-dependent pathway, apoA-I-mediated cAMP production required high level expression of functional ABCA1, and Tangier disease mutants have defective apoA-I-mediated cAMP signaling. These findings suggest that apoA-I may activate cAMP signaling through G protein-coupled ABCA1 transporter.

show abstract

Section: Discussionmentioning

confidence: 94%

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

Haidar

Denis

Marcil

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Furthermore, during the course of our studies, two other groups used yeast two-hybrid screens to isolate four proteins that bind the ABCA1 C terminus. Three of these proteins contain PDZ domains (␣1-and ␤2-syntrophin and Lin7) and one does not (22)(23)(24). The interaction of ␣1-syntrophin and ABCA1 was shown to require the final three amino acids of ABCA1, and, when co-transfected with ABCA1 in 293 cells, ␣1-syntrophin stabilized ABCA1 expression and increased efflux activity.…”

Section: Discussionmentioning

confidence: 99%

“…This diverse group of proteins contains one or more copies of a 90-amino acid domain that can bind the C termini of proteins ending in consensus motifs such as (S/T)XV-COOH, as is the case for class I PDZ binding domains (21). Indeed, using yeast two-hybrid screens and either the last 165 or 120 amino acids of the ABCA1 C terminus, two groups have recently reported the interaction of ABCA1 with three proteins containing PDZ domains (the ␣1 and ␤2 syntrophins and Lin7) and one non-PDZ protein (Fas-associated death domain protein) (22)(23)(24).…”

mentioning

confidence: 99%

ATP-binding Cassette Transporter A1 Contains a Novel C-terminal VFVNFA Motif That Is Required for Its Cholesterol Efflux and ApoA-I Binding Activities

Fitzgerald

Okuhira

Short

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The stimulation of cellular cholesterol and phospholipid efflux by apolipoprotein A-I is mediated by the activity of the ATP-binding cassette transporter A1 (ABCA1). Individuals with Tangier disease harbor lossof-function mutations in this transporter that have proven useful in illuminating its activity. Here, we analyze a mutation that deletes the last 46 residues of the 2261 amino acid transporter (⌬46) and eliminates its lipid efflux. As the final four amino acids of the C terminus represent a putative PDZ-binding motif, we initially characterized deletion mutants lacking only these residues. Although a moderate decline in lipid efflux was detected, this decline was not as profound as that seen in the ⌬46 mutant. Subsequent systematic analysis of the ABCA1 C terminus revealed a novel, highly conserved motif (VFVNFA) that was required for lipid efflux. Alteration of this motif, which is present in some but not all members of the ABCA family, did not prevent trafficking of the transporter to the plasma membrane but did eliminate its binding of apoA-I. Chimeric transporters, generated by substituting the C termini of either ABCA4 or ABCA7 for the endogenous terminus, demonstrated that ABCA1 could stimulate cholesterol efflux without its PDZ-binding motif but not without the VFVNFA motif. When a peptide containing the VFVNFA sequence was introduced into ABCA1-expressing cells, ABCA1-mediated lipid efflux was also markedly inhibited. These results indicate that the C-terminal VFVNFA motif of ABCA1 is essential for its lipid efflux activity. The data also suggest that this motif participates in novel protein-protein interactions that may be shared among members of the ABCA family.

show abstract

“…The observations that Cdc42-ABCA1 complex formation is absent in cells expressing a C-terminally truncated ABCA1 variant and that Cdc42-dependent signaling is abolished in these cells suggest that the C-terminal domain is indispensable for the interaction between ABCA1 and Cdc42. Several structural motifs mediating protein-protein interactions, such as the PDZ domain and the VFVNFA motif, were previously found within the ABCA1 C terminus (32,33). In this regard, it is of interest that several GDP exchange factors (GEFs), which increase the rate of GTP binding to Cdc42 and thereby specifically control its activity, contain the PDZ domain and are, therefore, potential ABCA1-interacting partners.…”

Section: Abca1 Transporter and Cdc42 Signalingmentioning

confidence: 99%

Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter

Nofer

Remaley

Feuerborn

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

It has been suggested that the signal transduction initiated by apolipoprotein A-I (apoA-I) activates key proteins involved in cholesterol efflux. ABCA1 serves as a binding partner for apoA-I, but its participation in apoA-I-induced signaling remains uncertain. We show that the exposure of human fibroblasts to ABCA1 ligands (apolipoproteins and amphipathic helical peptides) results in the generation of intracellular signals, including activation of the small G-protein Cdc42, protein kinases (PAK-1 and p54 JNK

show abstract

Molecular and Functional Interaction of the ATP-binding Cassette Transporter A1 with Fas-associated Death Domain Protein

Abstract: ATP-binding cassette transporter A1 (ABCA1) is a ma-

Cited by 25 publications

References 23 publications

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

ATP-binding Cassette Transporter A1 Contains a Novel C-terminal VFVNFA Motif That Is Required for Its Cholesterol Efflux and ApoA-I Binding Activities

Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter

Contact Info

Product

Resources

About