Publication

Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-kappaB Signaling

Kleino, Anni
Ramia, Nancy F.
Bozkurt, Gunes
Shen, Yanfang
Nailwal, Himani
Huang, Jing
Napetschnig, Johanna
Gangloff, Monique
Chan, Francis Ka-Ming
Wu, Hao
... show 2 more
Embargo Expiration Date
Abstract

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-kappaB 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.

Source

Kleino A, Ramia NF, Bozkurt G, Shen Y, Nailwal H, Huang J, Napetschnig J, Gangloff M, Chan FK, Wu H, Li J, Silverman N. Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-κB Signaling. Immunity. 2017 Oct 17;47(4):635-647.e6. doi: 10.1016/j.immuni.2017.09.011. PMID: 29045898; PMCID: PMC5665175. Link to article on publisher's site

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.1016/j.immuni.2017.09.011
PubMed ID
29045898
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources
Related Resources
Repository Citation
Rights
Distribution License