NT1 (DNT1, Spz2; UniProtKB:B7TB45) curation notes

Literature search (2026-11-06)

No deep-research API keys were available, so no provider deep-research file was generated and
just deep-research was not run. FlyBase has no hand-written gene description for NT1, so there
is no -deep-research-flybase.md file. Searches were made by hand from the GOA references, the
UniProt FUNCTION comment references and the references of the module
modules/neurotrophin_toll_signaling.yaml. Papers read from the local cache (full text unless
stated): PMID:19018662, PMID:23892553, PMID:24124519, PMID:28373203, PMID:28846707,
PMID:31088910, PMID:22022271 (fetched in this session), PMID:32066523, PMID:25741726.

Identity and structure

• DNT1 is a secreted Spätzle-family cystine-knot protein, named as the first Drosophila
  neurotrophin PMID:19018662.
• Prepro-protein with a signal peptide, pro-domain, cystine knot (CK) and a C-terminal tail
  PMID:19018662.
• Cleaved by furins; secreted both full length and cleaved [PMID:28373203 "DNT1 and 2 are cleaved
  intracellularly by conserved furins."; PMID:23892553 "DNT1 is secreted both as full-length and
  mature forms"].
• PANTHER PTHR23199:SF12 (UniProt DR line), PAINT node PTN002354018 shared with spz, spz5, spz6,
  spz3, spz4. No PAINT IRD/IKR losses on the lineage (just paint-losses DROME NT1).

Receptors and signaling

• Binds Toll-7 (and promiscuously Toll-6) PMID:23892553.
• Genetic epistasis: activated Toll-7 rescues DNT1 loss of function PMID:23892553.
• Mature DNT1 activates NF-kB (Dorsal/Dif) and ERK via Toll-6/7, while pro-DNT1 can activate JNK
  PMID:28373203.
• Binds Kek-6 in vitro (promiscuous) PMID:28846707.
• In vitro, the DNT1 (Spz-2) cystine knot binds Toll-1 and Toll-7 ectodomains and activates a
  drosomycin reporter in S2 cells PMID:31088910. No in vivo evidence places DNT1 in
  the Toll-1 immune pathway.
• Tracheal immunity: Spz2/DNT1 is the proposed ligand of Toll-8/Tollo in a module that dampens
  IMD-driven AMP expression in the trachea PMID:22022271.

Biological roles

• Neuronal survival, non-autonomous PMID:19018662.
• Motor axon targeting (ISNb/d, SN) PMID:19018662.
• No early CNS formation defect: PMID:19018662. The "central nervous system formation" annotations
  therefore over-state the phenotype.
• NMJ: DNT1 and DNT2 act redundantly in synaptogenesis/NMJ growth PMID:24124519.
  Synaptic plasticity is only speculated in PMID:19018662 ("Further functions of the DNTs could
  also include synaptic and neuronal activity, learning, and memory.").

Decisions summary

• MF: growth factor activity (GO:0008083) is the core ligand-activity term (child of receptor
  ligand activity). Toll binding rows MODIFY per projects/LIGANDS_IN_SIGNALING.md.
• BP: GO:0008063 Toll signaling pathway (receptor Toll-1 by definition) rests on an S2-cell
  reporter assay with Toll-1 and Toll-7; MODIFY to GO:0038179 neurotrophin signaling pathway,
  which is what the Toll-7 arm and the in vivo data (PMID:23892553, PMID:28373203) support.
• innate immune response IBA: kept as non-core (Tollo tracheal role, PMID:22022271).