Title
A natural loss-of-function mutation of MyD88 disrupts its ability to form Myddosomes
Academic Program
Interdisciplinary Graduate Program
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2011-04-01
Document Type
Article
Disciplines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
Abstract
Myeloid differentiation protein 88 (MyD88) is a key signaling adapter in Toll-like receptor (TLR) signaling. MyD88 is also one of the most polymorphic adapter proteins. We screened the reported non-synonymous coding mutations in MyD88 to identify variants with altered function. In reporter assays, a death domain variant, S34Y, was found to be inactive. Importantly, in reconstituted macrophage-like cell lines derived from knockout mice, MyD88 S34Y was severely compromised in its ability to respond to all MyD88-dependent TLR ligands. Unlike wild type MyD88, S34Y is unable to form distinct foci in the cells but is present diffused in the cytoplasm. We observed that IRAK4 colocalizes with MyD88 in these aggregates and thus these foci appear to be Myddosomes. The MyD88 S34Y loss of function mutant demonstrates how proper cellular localization of MyD88 to the Myddosome is a feature required for MyD88 function.
DOI of Published Version
10.1074/jbc.M110.199653
Source
Kamalpreet Nagpal K, Plantinga TS, Sirois CM, Monks BG, Latz E, Netea MG, Golenbock DT. (2011). Natural Loss-of-function Mutation of Myeloid Differentiation Protein 88 Disrupts Its Ability to Form Myddosomes. J Biol Chem. 2011 Apr 1;286(13):11875-82. First Published on February 16, 2011, doi:10.1074/jbc.M110.199653.
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
21325272
Repository Citation
Nagpal K, Plantinga TS, Sirois CM, Monks BG, Latz E, Netea MG, Golenbock DT. (2011). A natural loss-of-function mutation of MyD88 disrupts its ability to form Myddosomes. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1074/jbc.M110.199653. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1680