Toll-6 (Q9VUN0, FBgn0036494) curation notes

Literature search (2026-11-06)

No deep-research API keys were available, so no -deep-research-<provider>.md file
was generated. Searches run instead:

• PubMed Toll-6 Drosophila (23 hits: 42455660, 41656993, 40551010, 39704728,
  38838299, 38650964, 35732124, 35134382, 31477571, 30745142, 30361090, 28846707,
  28405401, 28373203, 27502486, 26150191, 25741726, 25363762, 23892553, 21158756,
  19602393, 12084571, 10973475). 38838299, 28405401, 19602393 concern the D42-GAL4
  driver inserted near toll-6 and are not about Toll-6 function; 12084571 is a
  silkworm Toll; 26150191 is a commentary.
• Newly cached with just fetch-pmid: 27502486, 35134382, 21158756, 15179511,
  35732124, 31477571, 40551010, 41656993, 38650964, 42455660, 12617819.
• FlyBase hand-written description (Toll-6-deep-research-flybase.md).

Neurotrophin receptor (core)

• Toll-6 and Toll-7 are receptors for Drosophila neurotrophins DNT1 (Spz2, NT1) and
  DNT2 (Spz5) PMID:23892553.
• Binding: PMID:23892553;
  binding is promiscuous PMID:28373203.
• Loss of function: PMID:23892553
• Membrane localization: PMID:23892553.
• Signalling: MyD88-dependent survival PMID:28373203; DNT2 activates NF-kB through Toll-6 in S2 cells PMID:28373203; Toll-6 can also induce
  apoptosis (pupae), independently of MyD88 via Wek/Sarm/JNK; dSarm does not bind Toll-6
  directly PMID:28373203.
• Toll-6-dSARM-FoxO pathway in motoneurons, microtubule dynamics, axon transport and
  structural plasticity PMID:27502486.

Synaptic plasticity

• NMJ: DNT2 from muscle acts on Kek-6 and Toll-6 in motoneurons PMID:28846707; "Toll-6 is required for active zone formation" (PMID:28846707).
• Dopaminergic circuit in adult brain PMID:39704728.
• Toll-receptor map underlying adult brain structural plasticity (PMID:32066523; Toll-2
  focus, cached but not cited in the review).

Wiring (olfactory)

• PMID:25741726. Toll-6 acts in
  PNs; it also non-autonomously affects VA1d ORN axon targeting. Cytoplasmic domain is
  dispensable PMID:25741726. So this wiring role is
  a cell-surface recognition role, not neurotrophin signalling via TIR.
• ER proteins Meigo and Gp93 regulate Toll-6 localization in PNs for dendrite targeting
  (PMID:35134382, abstract only).

Embryonic convergent extension

• Positional Toll code: PMID:25363762 and PMID:25363762. Toll-6 is one of three redundant stripe-expressed receptors; non-core.
• Long Tolls (Toll-2, -6, -7, -8) mediate interface surveillance in imaginal discs
  (PMID:41656993); striped LRR proteins and compartment boundaries (PMID:38650964). Not
  annotated.

Other contexts (not annotated, peripheral)

• Glia: neuronal apoptosis processes Spz5, which activates a dSARM-mediated Toll-6 pathway
  in glia controlling Draper expression PMID:30745142.
• Tumour models: Toll-6 required for tumour cell migration/invasion via JNK (PMID:31477571);
  fat-body Spz5 acting via Toll-6/alpha-Spectrin/Hippo in cell competition (PMID:35732124,
  abstract only); adipose Spz5-Toll-6-Hh in tumour progression (PMID:40551010); Upd3/Spz5/
  Toll-6 in bitter taste neurons (PMID:42455660, abstract only). These are all Spz5-Toll-6
  signalling in different cell types; consistent with the receptor function, not separate
  molecular functions.
• Immunity: Toll-6 mutants are viable and have no AMP induction defect PMID:21158756; UniProt records normal AMP induction
  in Toll-6 mutants.

PANTHER placement and the Slit-node IBAs

• UniProt DR PANTHER: PTHR24366:SF96 (HMM). PANTHER 19 tree: PTHR45836:SF8 "TOLL-LIKE
  RECEPTOR 6" inside the SLIT HOMOLOG family, hence IBAs from Slit nodes PTN002911633
  (Roundabout binding, heparin binding; Bilateria) and PTN002911625 (axon guidance; family
  root). interpro/panther/PTHR45836/PTHR45836-review.yaml already flags PTN002911633 as
  NEEDS_PRUNING for SF8 (Roundabout binding).
• Biological argument: Toll-6 is an LRR + TM + TIR receptor (UniProt: signal 1..14,
  TM 1058..1078, TIR 1111..1244) of the Toll-like receptor family; it has none of the Slit
  EGF repeats, laminin-G or C-terminal cystine-knot domains. Its closest paralogs are the
  long Tolls 18w/Toll-2, Toll-7, Toll-8 PMID:21158756. Placement in the Slit clade is an LRR-driven tree artifact.
  Robo binding is a Slit ligand property; no study reports Toll-6/Robo interaction ->
  REMOVE. Heparin binding is untested for Toll-6; LRR ectodomains can bind heparin, so
  MARK_AS_OVER_ANNOTATED rather than REMOVE. Axon guidance is independently true for Toll-6
  (motor axon targeting, PMID:23892553; VA1d ORN axon targeting, PMID:25741726) so the IBA
  row is accepted on that evidence despite the wrong ancestral source.
• just paint-losses DROME Toll-6: no IRD/IKR on lineage (Q9VUN0 not a leaf of PTHR24366).

Signal transduction IMP (PMID:31088910)

Full text cached; Toll-6 appears only in citations of McIlroy 2013 and of a Toll-1/TIR
chimera study. I could not find Toll-6 data in the cached text (possibly supplementary).
Row left UNDECIDED; the IEA row is modified to neurotrophin signaling pathway.