hbt

UniProt ID: Q9VK03
Organism: Drosophila melanogaster
Review Status: DRAFT
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Gene Description

Headbutt (hbt, CG43778) is a Drosophila multipass membrane protein of the Rost family (PANTHER PTHR12242, subfamily SF49), distantly related to Rolling stone, which is required for myoblast fusion. The gene encodes four products; Q9VK03 (isoform D, 451 aa) is an N-terminally truncated form identical to residues 513-963 of the 1003-aa canonical isoform E, and it retains the complete Rost region with six predicted transmembrane helices followed by a disordered Gly-rich tail. In the larva, an endogenous GFP knock-in shows Headbutt in non-neuronal support cells: sheath (thecogen-type) cells that wrap sensory dendrites in the terminal and dorsal organs, glia ensheathing chordotonal neurons, and a glia-like sheath around the brain and ventral nerve cord. hbt mutants have a strongly reduced gentle head-touch response and reduced calcium responses in terminal-organ chordotonal neurons, so Headbutt acts from these surrounding cells to support neuronal mechanosensitivity. Its molecular activity is unknown; a distant, profile-level resemblance of the family to the AIG1/ADTRP threonine hydrolases has been noted but not tested.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003674 molecular_function
ND
GO_REF:0000015
ACCEPT
Summary: No molecular activity has been established for Headbutt; the ND statement still holds.
Reason: The only gene-specific study (PMID:32761438; PMC full text read, local cache abstract-only) characterises a touch phenotype and the cellular expression pattern and states that the molecular/cellular function of CG43778 had not been studied. Family membership (Rost / PTHR12242) does not supply an activity: the characterised family member Rolling stone (SF46, a different subfamily) has a genetic role in myoblast fusion but no defined biochemical activity, and the HHpred-level resemblance of PTHR12242 to the AIG1/ADTRP FAHFA hydrolases (PMID:27018888) involves a different PANTHER family and could not be reproduced by pairwise alignment (hbt-bioinformatics/RESULTS.md). Accepting the ND is correct.
Supporting Evidence:
file:DROME/hbt/hbt-bioinformatics/RESULTS.md
Result: inconclusive; no hydrolase activity is inferred for hbt.
PMID:27018888
The HHpred search results, however, uncovered a distinct set of uncharacterized AIG1/ADTRP-like proteins that possess the conserved Thr and His residues and are found in non-mammalian eukaryotic organisms (Panther family PTHR12242; members in insects, plants, protozoa, and other non-vertebrates)
GO:0008150 biological_process
ND
GO_REF:0000015
MODIFY
Summary: The 2012 ND statement is superseded: a 2020 study shows hbt is required for larval head-touch sensitivity, and FlyBase now annotates the gene (on canonical isoform E) to regulation of sensory perception by IMP.
Reason: Zhang et al. 2020 (PMID:32761438) found CG43778 in a larval head-touch screen, named it headbutt, and showed with a MiMIC insertion, a CRISPR full knockout and their trans-heterozygote that loss of hbt halves the gentle-touch response and reduces Ca2+ responses of terminal-organ chordotonal neurons. Headbutt is expressed in sheath/glial cells wrapping the sensory dendrites, not in the neurons, which fits a regulatory role in mechanosensation rather than participation in force transduction. FlyBase attached the resulting IMP to GO:0051931 on the canonical product A0A6H2EJZ8; the knockout removes all isoforms and Q9VK03 carries the whole shared conserved core, so the gene-level process applies to this product too. GO:0051931 regulation of sensory perception is the term the curator chose and is as specific as the evidence (a behavioural and neuronal-response phenotype with a non-neuronal site of expression) supports. The publisher does not permit XML full-text download, so the local cache is abstract-only (the Letter has no abstract text); the findings were read from the PMC HTML full text and are summarised in the notes file, and only the title can be quoted verbatim here.
Proposed replacements: regulation of sensory perception
Supporting Evidence:
PMID:32761438
Molecular Basis for Cephalic Mechanosensitivity of Drosophila Larvae
GO:0016020 membrane
ISS
GO_REF:0000024
ACCEPT
Summary: Membrane localisation is well supported by the six-helix Rost-family architecture.
Reason: The ISS is from Rolling stone (FBgn0011705), a PTHR12242 family member in a different subfamily (SF46) whose membrane association was shown biochemically (enrichment in embryonic membrane fractions, PMID:9230076). Membrane location is a family-level property (the shared Rost region with six transmembrane helices is complete in Q9VK03 and 30.7% identical to Rost over 218 residues), so the transfer is sound, and PAINT independently places membrane at a PTHR12242 ancestral node (PTN001387085) for the canonical hbt product. Which membrane is not known: the GFP knock-in shows tube- and sheath-like structures around dendrites and glia but was not resolved to plasma or internal membranes, so the general term is as precise as the evidence allows.
Supporting Evidence:
file:DROME/hbt/hbt-uniprot.txt
FT TRANSMEM 40..63 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius"
file:DROME/hbt/hbt-uniprot.txt
DR Pfam; PF21534; Rost; 1.
PMID:9230076
the deduced protein sequence is in accordance with a transmembrane protein, which agrees with the enrichment of Rost in the membrane fraction of Drosophila embryos
file:DROME/hbt/hbt-bioinformatics/RESULTS.md
Isoform D retains the entire Rost (PF21534) region and all six predicted transmembrane helices

Core Functions

Multipass Rost-family membrane protein of sensory sheath cells and glia that is required for normal larval head-touch sensitivity and for full mechanically evoked responses of terminal-organ chordotonal neurons, acting from the cells that surround the sensory dendrites. Its molecular activity is unknown.

Cellular Locations:
Supporting Evidence:
  • PMID:32761438
    Molecular Basis for Cephalic Mechanosensitivity of Drosophila Larvae
  • file:DROME/hbt/hbt-bioinformatics/RESULTS.md
    Isoform D retains the entire Rost (PF21534) region and all six predicted transmembrane helices

References

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Suggested Questions for Experts

Q: Does the PTHR12242 (Rost) family, including Headbutt, retain the catalytic Thr and His of the AIG1/ADTRP hydrolases at structurally equivalent positions, and does Headbutt react with fluorophosphonate probes?

Q: Which hbt isoforms are expressed in the larval sheath cells and glia, and is the N-terminally truncated isoform D sufficient to rescue the hbt touch defect?

Q: Is the FlyBase IMP to regulation of sensory perception (currently on isoform E) intended to apply to all hbt products, given that the knockout removes every isoform?

Suggested Experiments

Experiment: Express isoform D (Q9VK03) and isoform E separately in sheath cells (prospero-Gal4) of hbt knockout larvae and test rescue of the gentle-touch response and chordotonal Ca2+ responses; in parallel mutate candidate conserved Thr/His residues of the Rost region and test activity-based probe labelling of tagged Headbutt in membrane fractions.

Deep Research

Falcon

(hbt-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(hbt-notes.md)

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Bioinformatics Results

(RESULTS.md)

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