PUBLICATION
A Unique Feature of Toll/IL-1 Receptor Domain-Containing Adaptor Protein Is Partially Responsible for Lipopolysaccharide Insensitivity in Zebrafish with a Highly Conserved Function of Myd88
- Authors
- Liu, Y., Li, M., Fan, S., Lin, Y., Lin, B., Luo, F., Zhang, C., Chen, S., Li, Y., and Xu, A.
- ID
- ZDB-PUB-100820-8
- Date
- 2010
- Source
- Journal of immunology (Baltimore, Md. : 1950) 185(6): 3391-3400 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/chemistry
- Adaptor Proteins, Signal Transducing/isolation & purification
- Adaptor Proteins, Signal Transducing/physiology*
- Amino Acid Motifs/immunology
- Amino Acid Sequence
- Animals
- Conserved Sequence/immunology*
- Humans
- Lipopolysaccharides/toxicity*
- Membrane Glycoproteins/chemistry
- Membrane Glycoproteins/isolation & purification
- Membrane Glycoproteins/physiology*
- Molecular Sequence Data
- Myeloid Differentiation Factor 88/physiology*
- NF-kappa B/metabolism
- Phosphatidylinositol 4,5-Diphosphate/chemistry
- Phosphatidylinositol 4,5-Diphosphate/metabolism
- Protein Binding/immunology
- Receptors, Interleukin-1/chemistry
- Receptors, Interleukin-1/isolation & purification
- Receptors, Interleukin-1/physiology*
- Signal Transduction/immunology
- Toll-Like Receptors/physiology
- Zebrafish/immunology*
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/isolation & purification
- Zebrafish Proteins/physiology*
- PubMed
- 20702732 Full text @ J. Immunol.
Citation
Liu, Y., Li, M., Fan, S., Lin, Y., Lin, B., Luo, F., Zhang, C., Chen, S., Li, Y., and Xu, A. (2010) A Unique Feature of Toll/IL-1 Receptor Domain-Containing Adaptor Protein Is Partially Responsible for Lipopolysaccharide Insensitivity in Zebrafish with a Highly Conserved Function of Myd88. Journal of immunology (Baltimore, Md. : 1950). 185(6):3391-3400.
Abstract
MyD88 and Toll/IL-1R domain-containing adaptor protein (TIRAP) are required for the TLR4 response to LPS stimulation in mammals, but the functions of the two adaptors and their involvement in zebrafish insensitivity to LPS remains unknown. We present a functional analysis of zebrafish Myd88 and Tirap and suggest that Myd88 is more important than Tirap for the activation of Tlr-mediated NF-kappaB, which may be a novel mechanism of Myd88-dependent TLR signaling in teleosts. Zebrafish Tirap lacks the phosphatidylinositol 4,5-bisphosphate binding motif required for human TIRAP location and has leucine at position 233 rather than the conserved proline of human TIRAP, as well as 105 additional aa at the N terminus. Overexpression of zebrafish Tirap in HEK293T cells did not activate NF-kappaB and IFN-beta, but slightly activated NF-kappaB in carp leukocyte cells. Zebrafish Myd88 alone strongly induced the activation of NF-kappaB and IFN-beta both in HEK293T and carp leukocyte cells. The function of Myd88 was dependent on its cellular location and the proline in the Toll/IL-1R domain. Although zebrafish Tirap was distributed throughout the cell rather than localized to the cytoplasmic membrane, its impaired ability to activate downstream Tlr molecules was unlikely to be related to its location because chimera TIRAP with a human TIRAP N terminus and membrane-binding domain also did not activate NF-kappaB. However, the mutation of leucine to proline increased the ability of Tirap to activate NF-kappaB. We suggest that the zebrafish Tirap needs a longer N terminus to perform its function and could be partially responsible for the resistance to LPS in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping