What they found
TMEM145 is a newly identified transmembrane protein that forms the core of TM-ACs (tectorial membrane attachment crowns) on outer hair cell stereocilia. Without TMEM145, stereocilin is lost from OHC stereocilia, the hair bundle physically disconnects from the tectorial membrane, and profound hearing loss results. TMEM145 appears to act as an anchor or scaffold that retains stereocilin at the stereocilia tip — not just a passenger in the complex.
How this applies to mini-STRC
This changes the structural model for mini-STRC design. Stereocilin doesn’t sit at the TM-AC alone — it depends on TMEM145 for localization. Mini-STRC (residues 700–1775) must preserve the TMEM145-binding interface, or the truncated protein will express but fail to localize correctly. This is the critical test: does the truncated region contain the TMEM145 interaction domain? Computational priority: AlphaFold-Multimer model of STRC-TMEM145 complex, then map which STRC residues form the interface, then verify those residues fall within our 700–1775 window.
Key numbers
- Without TMEM145: stereocilin lost from OHC stereocilia entirely
- Result: hair bundle disconnects from tectorial membrane → profound HL
- TMEM145 is transmembrane (OHC-expressed), stereocilin is extracellular
Links
Connections
- STRC Mini-STRC Single-Vector Hypothesis — TMEM145 as anchor; mini-STRC must preserve binding interface
- STRC Stereocilia Bundle Mechanics Model — TM attachment depends on TMEM145–stereocilin link
[see-also]Derstroff et al 2026 TMEM145 Paper — full analysis note
Numbers that matter (2026-04-23 audit)
SPR/BLI Kd for STRC × TMEM145 — NOT found in Derstroff 2026 Neuron.
Full text and PubMed abstract checked. Methods used for STRC–TMEM145 interaction:
- Co-immunoprecipitation (CoIP): qualitative, detected interaction, no Kd
- NanoSPD pull-down assay: qualitative, detected TMEM145–tubby interaction, no Kd
- AlphaFold Multimer: ipTM 0.79 and 0.71 (computational confidence, not binding affinity)
The model’s claim of Kd = 10 nM has no experimental SPR/BLI source in this paper. Supplementary contains only Fig S11 (band quantification from CoIP) — no biophysical binding measurements.
Parallel TMEM145 paper (different group): Nature Communications 2025, DOI 10.1038/s41467-025-67011-0 — also no SPR/BLI Kd reported. Also uses pull-down and co-IP.
Bottom line: No published SPR/BLI Kd for STRC × TMEM145 exists in the literature as of 2026-04-23. The 10 nM figure in the model is unsourced — either inferred from AF3 ipTM or fabricated. This is the most critical gap in Phase 1 parameterization.