Regulation of adherence and virulence by the Entamoeba histolytica lectin cytoplasmic domain, which contains a beta2 integrin motif.
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.
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
R R
RR
Vines
G
G
Ramakrishnan
J B
JB
Rogers
L A
LA
Lockhart
B J
BJ
Mann
W A
WA
Petri
D000595:Amino Acid Sequence; D000818:Animals; D018821:CD18 Antigens / Q000737:chemistry*; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D004748:Entamoeba histolytica / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D005849:Gerbillinae; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000502:physiology; D008101:Liver Abscess, Amebic / Q000473:pathology / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D014162:Transfection; D014774:Virulence
D018821:CD18 Antigens; D037102:Lectins; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C052452:galactose inhibitable adherence protein, Entamoeba histolytica