ATP-Binding Cassette Transporter-1 Induces Rearrangement of Actin Cytoskeletons Possibly through Cdc42/N-WASP

Tsukamoto, Kosuke; Hirano, Ken‐ichi; Tsujii, K.; Ikegami, Chiaki; Zhang, Zhongyan; Nishida, Yusuke; Ohama, Tohru; Matsuura, Fumihiko; Yamashita, Shizuya; Matsuzawa, Yūji

doi:10.1006/bbrc.2001.5575

Cited by 58 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 96%

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: 96%

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

“…Cdc42 forms complexes with proteins that control the cytoskeletal architecture and vesicular transport (75). Initially it was observed that Tangier fibroblasts lacking ABCA1 displayed an abnormal actin cytoskeleton that was associated with decreased expression and activity of the Cdc42 (76,77). Forced expression of Cdc42 was shown to enhance apoA-Imediated cholesterol efflux, whereas expression of a dominant negative Cdc42 impaired this efflux (59,76).…”

Section: Rho Gtpasesmentioning

confidence: 99%

The Interaction of ApoA-I and ABCA1 Triggers Signal Transduction Pathways to Mediate Efflux of Cellular Lipids

Zhao

Yin

et al. 2011

Mol Med

View full text Add to dashboard Cite

Reverse cholesterol transport (RCT) has been characterized as a crucial step for antiatherosclerosis, which is initiated by ATPbinding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I). However, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as the lipidation of apoA-I mediated by ABCA1. ApoA-I increases the levels of ABCA1 protein markedly. In turn, ABCA1 can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate posttranslational ABCA1 activity or lipid transport activity. The key signaling molecules in these processes include protein kinase A (PKA), protein kinase C (PKC), Janus kinase 2 (JAK2), Rho GTPases and Ca 2+ , and many factors also could influence the interaction of apoA-I with ABCA1. This review will summarize these mechanisms for the apoA-I interaction with ABCA1 as well as the signal transduction pathways involved in these processes.

show abstract

“…14 Furthermore, ABCA1 appears to interact with several important components of vesicular traffic machinery such as cdc42, a small G protein, and the beta-subunit of coat protein I (COPI-I) coatomer complex essential for the formation of transport vesicles. 15 cle formation by ABCA1 may also be important to exocytosis of apo E, which is able to initiate cholesterol efflux locally and thereby to promote reverse cholesterol transport. 17 …”

Section: Hdl and Reverse Cholesterol Transportmentioning

confidence: 99%

HDL Cholesterol and Protective Factors in Atherosclerosis

2004

View full text Add to dashboard Cite

Abstract-A low level of high-density lipoprotein cholesterol (HDL-C) is an important risk factor for cardiovascular disease. Epidemiological and clinical studies provide evidence that HDL-C levels are linked to rates of coronary events. The cardioprotective effects of HDL-C have been attributed to its role in reverse cholesterol transport, its effects on endothelial cells, and its antioxidant activity. Although some clinical trials suggest a benefit of raising HDL-C to reduce risk, further studies are needed, and HDL-C is still not considered a primary target of therapy in the National Cholesterol Education Program guidelines. However, HDL-C should be considered as part of the patient's overall profile of established risk factors in determining treatment strategies. T he association between low levels of high-density lipoprotein cholesterol (HDL-C) and an increased risk for cardiovascular disease has been well established through epidemiological and clinical studies. 1 This relationship is supported by the potential antiatherogenic properties of HDL, including its mediation of reverse cholesterol transport, in which cholesterol from peripheral tissues is returned to the liver for excretion in the bile. 2 This review considers the potential mechanisms by which HDL-C may exert its antiatherogenic effects, discusses disorders of HDL and how to interpret them in the clinical setting, and presents current and potential treatment strategies for patients with low HDL-C. Structure and Metabolism of HDL and Relation to Potential Mechanisms of BenefitOverview of HDL Structure and Heterogeneity HDL is a class of heterogeneous lipoproteins containing approximately equal amounts of lipid and protein. 1 HDL particles are characterized by high density (Ͼ1.063 g/mL) and small size (Stoke's diameter ϭ5 to 17 nm). The various HDL subclasses vary in quantitative and qualitative content of lipids, apolipoproteins, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Most of apolipoprotein A-I (apo A-I), the predominant HDL protein, migrates in agarose gels with ␣-electrophoretic mobility and is designated ␣-LpA-I. This fraction accounts for almost all of the cholesterol quantified in the clinical laboratory as HDL-C. ␣-HDL can be further fractionated by density into HDL 2 and HDL 3 , by size, or by apolipoprotein composition. Approximately 5% to 15% of apo A-I in human plasma is associated with particles with pre-␤-electrophoretic mobility. These can be further differentiated into pre-␤ 1 -LpA-I, pre-␤ 2 -LpA-I, and pre-␤ 3 -LpA-I particles. These lipid-poor particles are increased in extravascular compartments where reverse cholesterol transport takes place. 3 The origin of HDL particles with pre-␤-electrophoretic mobility is not entirely clear. Several mechanisms have been proposed, including direct secretion into plasma from hepatocytes or enterocytes; release during the interconversion of various HDL subpopulations by phospholipid transfer protein (PLTP), cholesteryl ...

show abstract

ATP-Binding Cassette Transporter-1 Induces Rearrangement of Actin Cytoskeletons Possibly through Cdc42/N-WASP

Cited by 58 publications

References 43 publications

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

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

The Interaction of ApoA-I and ABCA1 Triggers Signal Transduction Pathways to Mediate Efflux of Cellular Lipids

HDL Cholesterol and Protective Factors in Atherosclerosis

Contact Info

Product

Resources

About