MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity

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.

Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development

“…In addition, we found that nfki-1 and ikb-1 mutants are more resistant to starvation than wild type animals. This phenotype could be related with the recently demonstrated interaction of NFKI-1 with cytoplasmic MALT-1, which regulate resistance to environmental stresses 39 .…”

“…We challenged the reporter strain in different ways, but we did not find a condition, besides overexpression, that increases the presence of NFKI-1 in the nuclei. Supporting the nuclear location of NFKI-1, a recent study detected NFKI-1 in the nuclear fraction of C. elegans and a protein-protein interaction with the histone methyl transferase CBP-1/P300 39 .…”

Defining the combinatorial space of PKC::CARD‐CC signal transduction nodes

“…However, MALT1 inhibition may be a double‐edged sword as MALT1 deficiency in mice and humans has been linked with immunodeficiency as well as autoimmunity [17–25]. MALT1 also seems to be able to be activated independently of CBM‐complex formation, which is highlighted by its presence in organisms lacking BCL10 and CARD‐CC homologs [10,26] and by its activation by overexpression of TRAF6 or viral effector proteins [27,28]. The physiological role and relevance of CBM‐independent MALT1 activity is, however, unknown.…”

Transcriptional Control Of Calmodulin By CAMTA Regulates Neural Excitability

“…O2-and CO2-response assays were performed as described previously 46 Chemotaxis assays were performed as previously described (Bargmann et al, 1993) with minor modifications. 9 cm assay plates were made with 2% Bacto Agar, 1mM CaCl2, 1mM MgSO4 and 25mM K2HPO4 pH 6.…”

“…The expression pattern of CAMT-1(fosmid)-GFP was imaged as previously described 46 on an Inverted Leica SP8 confocal microscope using a 63x/1.20 N.A.…”