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Insights into the fate of the N-terminal amyloidogenic polypeptide of ApoA-I in cultured target cells.

Arciello A, De Marco N, Del Giudice R, Guglielmi F, Pucci P, Relini A, Monti DM, Piccoli R - J. Cell. Mol. Med. (2011)

Bottom Line: Apolipoprotein A-I (ApoA-I) is an extracellular lipid acceptor, whose role in cholesterol efflux and high-density lipoprotein formation is mediated by ATP-binding cassette transporter A1 (ABCA1).In this paper, rat cardiomyoblasts were used as target cells to analyse binding, internalization and intracellular fate of the fibrillogenic polypeptide in comparison to full-length ApoA-I.We provide evidence that the polypeptide: (i) binds to specific sites on cell membrane (K(d) = 5.90 ± 0.70 × 10(-7) M), where it partially co-localizes with ABCA1, as also described for ApoA-I; (ii) is internalized mostly by chlatrin-mediated endocytosis and lipid rafts, whereas ApoA-I is internalized preferentially by chlatrin-coated pits and macropinocytosis and (iii) is rapidly degraded by proteasome and lysosomes, whereas ApoA-I partially co-localizes with recycling endosomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, University of Naples Federico II, School of Biotechnological Sciences, Naples, Italy.

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Schematic representation of internalization routes and intracellular fates of [1–93]ApoA-I and ApoA-I in H9c2 cells. Lipid rafts are coloured in red; chlatrin-coated pits in green; macropinocytosis in blue. Rab4 vesicles are represented by green circles. N: nucleus; P: proteasome; L: lysosomes.
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fig08: Schematic representation of internalization routes and intracellular fates of [1–93]ApoA-I and ApoA-I in H9c2 cells. Lipid rafts are coloured in red; chlatrin-coated pits in green; macropinocytosis in blue. Rab4 vesicles are represented by green circles. N: nucleus; P: proteasome; L: lysosomes.

Mentions: In conclusion, the data reported here reveal that ApoA-I fibrillogenic fragment, the main constituent of amyloid fibrils, binds to target cells, is internalized and rapidly degraded. The internalization routes, intracellular pathways and degradation mechanisms of full-length ApoA-I and its fibrillogenic polypeptide are not fully coincident, as schematically depicted in Scheme 1.


Insights into the fate of the N-terminal amyloidogenic polypeptide of ApoA-I in cultured target cells.

Arciello A, De Marco N, Del Giudice R, Guglielmi F, Pucci P, Relini A, Monti DM, Piccoli R - J. Cell. Mol. Med. (2011)

Schematic representation of internalization routes and intracellular fates of [1–93]ApoA-I and ApoA-I in H9c2 cells. Lipid rafts are coloured in red; chlatrin-coated pits in green; macropinocytosis in blue. Rab4 vesicles are represented by green circles. N: nucleus; P: proteasome; L: lysosomes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373434&req=5

fig08: Schematic representation of internalization routes and intracellular fates of [1–93]ApoA-I and ApoA-I in H9c2 cells. Lipid rafts are coloured in red; chlatrin-coated pits in green; macropinocytosis in blue. Rab4 vesicles are represented by green circles. N: nucleus; P: proteasome; L: lysosomes.
Mentions: In conclusion, the data reported here reveal that ApoA-I fibrillogenic fragment, the main constituent of amyloid fibrils, binds to target cells, is internalized and rapidly degraded. The internalization routes, intracellular pathways and degradation mechanisms of full-length ApoA-I and its fibrillogenic polypeptide are not fully coincident, as schematically depicted in Scheme 1.

Bottom Line: Apolipoprotein A-I (ApoA-I) is an extracellular lipid acceptor, whose role in cholesterol efflux and high-density lipoprotein formation is mediated by ATP-binding cassette transporter A1 (ABCA1).In this paper, rat cardiomyoblasts were used as target cells to analyse binding, internalization and intracellular fate of the fibrillogenic polypeptide in comparison to full-length ApoA-I.We provide evidence that the polypeptide: (i) binds to specific sites on cell membrane (K(d) = 5.90 ± 0.70 × 10(-7) M), where it partially co-localizes with ABCA1, as also described for ApoA-I; (ii) is internalized mostly by chlatrin-mediated endocytosis and lipid rafts, whereas ApoA-I is internalized preferentially by chlatrin-coated pits and macropinocytosis and (iii) is rapidly degraded by proteasome and lysosomes, whereas ApoA-I partially co-localizes with recycling endosomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, University of Naples Federico II, School of Biotechnological Sciences, Naples, Italy.

Show MeSH
Related in: MedlinePlus