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.
Vines
R R
RR
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
Ramakrishnan
G
G
Rogers
J B
JB
Lockhart
L A
LA
Mann
B J
BJ
Petri
W A
WA
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