Functional analysis of AeSCP‐2 using gene expression knockdown in the yellow fever mosquito, <i>Aedes aegypti</i>

Blitzer, E. J.; Vyazunova, Irina; Lan, Qing

doi:10.1111/j.1365-2583.2005.00560.x

Cited by 56 publications

(80 citation statements)

References 30 publications

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“…Sterol carrier protein-2 (SCP-2) has been identified in several insect species 9,[30][31][32] and is thought to mediate cholesterol uptake and intracellular transportation. 9,11,12,33) Also, several chemical compounds that strongly inhibit the binding between cholesterol and AeSCP-2 (SCP-2 in Aedes aegypti) have been identified.…”

Section: Discussionmentioning

confidence: 99%

“…Sterol carrier protein-2 (SCP-2) has been shown to be involved in cholesterol uptake and intracellular trafficking in insects. 11,12) By inhibiting cholesterol uptake and intracellular transportation, sterol carrier protein-2 inhibitors (SCPIs) exhibited larvicidal activity against several important insect pests, [6][7][8]13) whereas they showed no toxicity against mouse NmuMG cells or rats. 6,8) a-Mangostin, a major xanthone derivative in mangosteen (Garciana mangostana) (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Kim

Lan

2011

J. Pestic. Sci.

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a-Mangostin, a major xanthone derivative in mangosteen (Garcinia mangostana), has been proven to have a wide range of biological-activities. In this study, we assessed the larvicidal and antifeeding activities of a-mangostin using larvae and adults of the Colorado potato beetle, Leptinotarsa decemlineata Say. a-Mangostin showed larvicidal activity and growth inhibitory effects under non-choice feeding conditions. The LC 50 values with 7-, 14-and 23-day treatment were 63.66 (13.29-279.79) mM, 8.37 (2.67-20.27) mM and 4.09 (0.89-11.81) mM, respectively. Larval development was significantly delayed 3-8 days with a-mangostin treatment. The antifeeding activity of a-mangostin was also tested by leaf disc non-choice and choice methods against larvae and adults of L. decemlineata. a-Mangostin had stronger antifeeding-activity toward adults than toward larvae, whereas there was low lethality in adults associated with higher antifeeding indexes (AFIs). The larvicidal and antifeeding effects suggest that a-mangostin and related compounds should be explored for their potential as botanical insecticide alternatives for control of the Colorado potato beetle.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Kim

Lan

2011

J. Pestic. Sci.

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“…The expression of the yellow fever mosquito SCP-2 (AeSCP-2) and SCP-2-like genes (AeSCP-2-like1 and AeSCP-2-like2) is overlapped temporally and spatially in the larval stages, but only AeSCP-2 and AeSCP-2-like2 (AeSCP-2L2) genes are transcribed in adults (18,19). The ligand binding affinities of AeSCP-2 and AeSCP-2L2 are different: AeSCP-2 has substantially higher affinity (5.6 3 10 29 M) for cholesterol (20) than AeSCP-2L2 (2.6 3 10 26 M) (19).…”

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confidence: 99%

Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family members

Dyer

Wessely

Forest

et al. 2008

Journal of Lipid Research

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Mosquito sterol carrier protein-2 (AeSCP-2) and sterol carrier protein-2-like2 (AeSCP-2L2) are members of the SCP-2 protein family with similar expression profiles in the mosquito life cycle. In an effort to understand how lipids can be transported by different SCP-2 proteins, the three-dimensional crystal structure of AeSCP-2L2 was solved at 1.7 Å resolution. AeSCP-2L2 forms a dimer and binds three fatty acids, one of which resides in a position within the internal cavity at a right angle to the others. This first report of ligand-bound dimerized protein in the SCP-2 protein family indicates that the family has a much more divergent mode of interaction with ligands than previously reported. The potential function of AeSCP-2L2 was investigated via in vivo incorporation of [ 3 H]cholesterol and [ 3 H]palmitic acid. Overexpression of AeSCP-2L2 in mosquito cells leads to an increased uptake of free fatty acid, whereas knockdown of AeSCP-2L2 in adult females decreases the accumulation of free fatty acid in the fat body from a blood meal. In contrast, overexpression or knockdown of AeSCP-2L2 has no effect on cholesterol uptake. Our results suggest that the main function of AeSCP-2L2 is as a general intracellular fatty acid carrier, as opposed to having a dedicated role in cholesterol transport.-Dyer, D. H., V. Wessely, K. T. Forest, and Q. Lan. Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family members. J. Lipid Res. 2008. 49: 644-653.

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“…In insects, SCP-2 was shown to be involved in cholesterol uptake in the midgut in both larval and adult mosquitoes (10,11). Whereas in mice, knock-out of the SCP-2 had little effect on development, growth, mortality, or fertility (6), knockdown of SCP-2 expression in mosquitoes resulted in high mortality in developing adults and significantly lowered fertilities (10).…”

mentioning

confidence: 99%

“…Whereas in mice, knock-out of the SCP-2 had little effect on development, growth, mortality, or fertility (6), knockdown of SCP-2 expression in mosquitoes resulted in high mortality in developing adults and significantly lowered fertilities (10). Moreover, chemical inhibitors of A. aegypti SCP-2 showed remarkable specificity toward insects versus mammals (12,13).…”

mentioning

confidence: 99%

Differences in the Structure and Dynamics of the Apo- and Palmitate-ligated Forms of Aedes aegypti Sterol Carrier Protein 2 (AeSCP-2)

Singarapu

Radek

Tonelli

et al. 2010

Journal of Biological Chemistry

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Sterol carrier protein-2 (SCP-2) is a nonspecific lipid-binding protein expressed ubiquitously in most organisms. Knockdown of SCP-2 expression in mosquitoes has been shown to result in high mortality in developing adults and significantly lowered fertility. Thus, it is of interest to determine the structure of mosquito SCP-2 and to identify its mechanism of lipid binding. We report here high quality three-dimensional solution structures of SCP-2 from Aedes aegypti determined by NMR spectroscopy in its ligand-free state (AeSCP-2) and in complex with palmitate. Both structures have a similar mixed ␣/␤ fold consisting of a five-stranded ␤-sheet and four ␣-helices arranged on one side of the ␤-sheet. Ligand-free AeSCP-2 exhibited regions of structural heterogeneity, as evidenced by multiple two-dimensional 15 N heteronuclear single-quantum coherence peaks for certain amino acids; this heterogeneity disappeared upon complex formation with palmitate. The binding of palmitate to AeSCP-2 was found to decrease the backbone mobility of the protein but not to alter its secondary structure. Complex formation is accompanied by chemical shift differences and a loss of mobility for residues in the loop between helix ␣I and strand ␤A. The structural differences between the ␣I and ␤A of the mosquito and the vertebrate SCP-2s may explain the differential specificity (insect versus vertebrate) of chemical inhibitors of the mosquito SCP-2.

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Functional analysis of AeSCP‐2 using gene expression knockdown in the yellow fever mosquito, Aedes aegypti

Cited by 56 publications

References 30 publications

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Three-dimensional structure/function analysis of SCP-2-like2 reveals differences among SCP-2 family members

Differences in the Structure and Dynamics of the Apo- and Palmitate-ligated Forms of Aedes aegypti Sterol Carrier Protein 2 (AeSCP-2)

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