Toll-7 (Q7KIN0) — review notes
Batch 1 (Toll/TLR axis) of the INNATE_IMMUNITY project. Falcon deep research had not
started for this gene when the review was drafted; notes are built from the cached
GOA publications and the UniProt record.
Neurotrophin receptor (core)
Antiviral role and the PRR question
- Nakamoto et al. 2012 (Cherry lab): PMID:22464169; PMID:22464169; autophagy induction is NF-kB/MyD88 independent PMID:22464169.
- Moy et al. 2014 (same lab), RVFV: PMID:24374193; restriction is virus-specific (no phenotype with DCV, FHV, SINV).
- Chowdhury et al. 2019 (independent lab): Toll-7 ectodomain co-precipitates VSV, but so does Toll-1, and they note contrary data PMID:31088910. The contrary paper (their ref. 32) is not in the local cache and was not read.
- Assessment: Toll-7 is the only Drosophila Toll with direct pathogen-binding data. The binding evidence is co-precipitation of whole virions, no defined viral ligand molecule, no affinity or structural data, and the specificity control (Toll does not bind) is contradicted by Chowdhury et al. The GO:0038187 pattern recognition receptor activity (IC) and GO:0002752 cell surface PRR signaling pathway (IC) rows are therefore kept but as non-core, and flagged as a question; the direct observation GO:0046790 virion binding (IDA, two labs) is accepted.
Canonical Toll pathway / AMP induction: conflicting
- Chowdhury 2019: Spz-bound Toll-7 activates drosomycin promoter in S2 cells PMID:31088910.
- Against: PMID:10973475; PMID:24374193; and Nakamoto reports VSV-induced Toll-7 signalling is distinct from canonical Toll/IMD/JAK-STAT.
- Decision: GO:0008063 Toll signaling pathway and GO:0002225 positive regulation of antimicrobial peptide production (both IMP, PMID:31088910) -> UNDECIDED.
Project question 1 answer (Toll-7)
Yes — Toll-7 is the one gene in this trio carrying PRR-branch terms (GO:0038187 IC and
GO:0002752 IC, both FlyBase from PMID:22464169). No GO:0002224 (toll-like receptor
signaling pathway) term is attached. The PRR terms rest on a single lab's virion
co-precipitation data; I keep them as non-core rather than remove them, and raise
the definitional issue (whole-virion binding vs. a defined PAMP) as a question.
Falcon deep research (added after it completed)
- Deep research (file:DROME/Toll-7/Toll-7-deep-research-falcon.md) agrees that the antiviral assignment is contested: ["Toll-7's involvement in the response to viral infection remains unresolved and should not be treated as established functional annotation"]. This supports keeping GO:0038187 and GO:0002752 as non-core rather than core.
- It also reports that olfactory wiring is ligand- and TIR-independent: ["the known neurotrophin ligands DNT-1 and DNT-2 are dispensable for this ORN-PN matching function"]. The axon guidance annotation stands, but in olfactory wiring Toll-7 acts as a recognition molecule and not as a neurotrophin receptor.
- It summarises a 2024 iScience study (Zhang et al., "Maintaining Toll signaling in Drosophila brain is required to sustain autophagy for dopamine neuron survival") reporting that Toll-7 maintains basal brain autophagy through a MyD88-independent, Tube/Pelle/PP2A pathway, and that the TIR-7 domain induces drosomycin in S2 cells in a MyD88-dependent way. The PMID was not resolved or cached in this session, so it is not cited in the review. It is a candidate for a future positive regulation of autophagy / neuron survival annotation.