title: Defining the origins of the NOD-like receptor system at the base of animal evolution.
abstract: Distinguishing self from nonself and the onset of defense effector mechanisms upon recognition of pathogens are essential for the survival of all life forms in the animal kingdom. The family of nucleotide -binding and oligomeriszation domain-like receptors (NLRs) was first identified in vertebrates and comprises a group of pivotal sensor protein of the innate immune system for microbial cell wall components or danger signals. Here, we provide first evidence that early diverging metazoans have large and complex NLR repertoires. The cnidarian NACHT/NB-ARC genes include novel combinations of domains, and the number of one specific type (NB-ARC and tetratricopeptide repeat containing) in Hydra is particularly large. We characterize the transcript structure and expression patterns of a selected HyNLR, HyNLR type 1 and describe putative interaction partners. In a heterologous expression system, we show induced proximity recruitment of an effector caspase (HyDD-Caspase) to the HyNLR type 1 protein upon oligomerization indicating a potential role of caspase activation downstream of NLR activation in Hydra. These results add substantially to our understanding of the ancestral innate immune repertoire as well as providing the first insights into putative cytoplasmic defense mechanisms at the base of animal evolution.
authors.affiliation: Zoological Institute, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lange
authors.forename: Georg
authors.initials: G
authors.lastname: Hemmrich
authors.forename: Ulrich C
authors.initials: UC
authors.lastname: Klostermeier
authors.forename: Javier A
authors.initials: JA
authors.lastname: López-Quintero
authors.forename: David J
authors.initials: DJ
authors.lastname: Miller
authors.forename: Tasja
authors.initials: T
authors.lastname: Rahn
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Weiss
authors.forename: Thomas C G
authors.initials: TC
authors.lastname: Bosch
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020169:Caspases / Q000378:metabolism; D003198:Computer Simulation; D019143:Evolution, Molecular; D040461:Gene Components; D020869:Gene Expression Profiling; D006801:Humans; D006829:Hydra / Q000235:genetics* / Q000276:immunology; D007113:Immunity, Innate; D008957:Models, Genetic; D053472:Nod Signaling Adaptor Proteins / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D053472:Nod Signaling Adaptor Proteins; D020169:Caspases