Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-κB Signaling
| Autor: | Nancy F. Ramia, Jing Huang, Neal S. Silverman, Yanfang Shen, Johanna Napetschnig, Jixi Li, Hao Wu, Gunes Bozkurt, Monique Gangloff, Himani Nailwal, Francis Ka-Ming Chan, Anni Kleino |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Amyloid Necroptosis Amino Acid Motifs Immunology Gene Expression Receptors Cell Surface Peptidoglycan Biology Article Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression Animals Drosophila Proteins Immunology and Allergy Amino Acid Sequence Receptor Biological Phenomena Binding Sites Microscopy Confocal Innate immune system Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Models Immunological NF-kappa B Signal transducing adaptor protein Cell biology Drosophila melanogaster 030104 developmental biology Infectious Diseases chemistry Receptor-Interacting Protein Serine-Threonine Kinases Mutation Female Drosophila Carrier Proteins Sequence motif 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Immunity. 47:635-647.e6 |
| ISSN: | 1074-7613 |
| Popis: | Summary In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each contain a motif with some resemblance to the RIP Homotypic Interaction Motif (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids during necroptosis. Here we found that despite sequence divergence, these Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells. Amyloid formation was required for signaling downstream of Imd, and in contrast to the mammalian RHIMs, was not associated with cell death. Furthermore, amyloid formation constituted a regulatable step and could be inhibited by Pirk, an endogenous feedback regulator of this pathway. Thus, diverse sequence motifs are capable of forming amyloidal signaling platforms, and the formation of these platforms may present a regulatory point in multiple biological processes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|