| RRC ID |
65186
|
| Author |
Flynn SM, Chen C, Artan M, Barratt S, Crisp A, Nelson GM, Peak-Chew SY, Begum F, Skehel M, de Bono M.
|
| Title |
MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity.
|
| Journal |
Nat Commun
|
| Abstract |
Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17-MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.
|
| Volume |
11(1)
|
| Pages |
2099
|
| Published |
2020-4-29
|
| DOI |
10.1038/s41467-020-15872-y
|
| PII |
10.1038/s41467-020-15872-y
|
| PMID |
32350248
|
| PMC |
PMC7190641
|
| MeSH |
Animals
Behavior, Animal
Caenorhabditis elegans / drug effects
Caenorhabditis elegans / genetics
Caenorhabditis elegans / immunology*
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / metabolism*
Gene Expression Regulation / drug effects
Green Fluorescent Proteins / metabolism
Immunity* / drug effects
Interleukin-17 / metabolism*
Interneurons / drug effects
Interneurons / physiology
Longevity* / drug effects
Models, Biological
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / metabolism*
Neurons / drug effects
Neurons / metabolism*
Oxygen / pharmacology
Signal Transduction / drug effects
Subcellular Fractions / metabolism
Transgenes
|
| Resource |
| C.elegans |
tm2167
tm5866
tm3036
tm5218 |
