Abstract
Killing of human cells by the parasite Entamoeba histolytica requires adherence via an amebic cell surface lectin. Lectin activity in the parasite is regulated by inside-out signaling. The lectin cytoplasmic domain has sequence identity with a region of the beta2 integrin cytoplasmic tail implicated in regulation of integrin-mediated adhesion. Intracellular expression of a fusion protein containing the cytoplasmic domain of the lectin has a dominant negative effect on extracellular lectin-mediated cell adherence. Mutation of the integrin-like sequence abrogates the dominant negative effect. Amebae expressing the dominant negative mutant are less virulent in an animal model of amebiasis. These results suggest that inside-out signaling via the lectin cytoplasmic domain may control the extracellular adhesive activity of the amebic lectin and provide in vivo demonstration of the lectin's role in virulence.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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CD18 Antigens / chemistry*
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CHO Cells
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Cell Adhesion
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Cricetinae
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Entamoeba histolytica / genetics
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Entamoeba histolytica / pathogenicity*
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Entamoeba histolytica / physiology*
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Gerbillinae
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Humans
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Lectins / chemistry
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Lectins / physiology
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Liver Abscess, Amebic / pathology
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Liver Abscess, Amebic / physiopathology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / physiology*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protozoan Proteins / biosynthesis
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Protozoan Proteins / chemistry
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Protozoan Proteins / physiology*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Transfection
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Virulence
Substances
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CD18 Antigens
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Lectins
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Membrane Glycoproteins
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Protozoan Proteins
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Recombinant Proteins
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galactose inhibitable adherence protein, Entamoeba histolytica