Zhang et al. 2012 — Slow protein turnover in hair-cell stereocilia
Citation: Duan-Sun Zhang, Valeria Piazza, Benjamin J Perrin, Agnieszka K Rzadzinska, J Collin Poczatek, Mei Wang, Haydn M Prosser, James M Ervasti, David P Corey, Claude P Lechene. “Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia.” Nature 481:520–524, 2012. PMID 22246323. DOI 10.1038/nature10745.
Numbers that matter
| Parameter | Value | Cell type / condition | PMC full text |
|---|---|---|---|
| Frog saccular stereocilia protein incorporation | < 0.3%/day | Adult frog sacculus in vivo | PMC3267870 |
| Mouse cochlear stereocilia protein incorporation | ~2%/day initially | Adult mouse cochlea in vivo | PMC3267870 |
| Mouse vestibular stereocilia protein incorporation | < 3%/day initially | Adult mouse utricle in vivo | PMC3267870 |
| Neonatal mouse stereocilia protein incorporation | < 9%/day | P0–P10 mouse bundles | PMC3267870 |
| Pulse-chase duration tracked | up to 150 days | Mouse cochlear actin shaft | PMC3267870 |
| After 5 months 15N incorporation | < 60% total | Mouse cochlear stereocilia | PMC3267870 |
| Tip vs shaft comparison (frog, 32 d) | Tips 12.5% vs shafts 6.1% | Frog bundle | PMC3267870 |
| Treadmilling observed | No | All species/ages tested | PMC3267870 |
Full text verified via PMC3267870 (2026-04-25).
Core finding
Multi-isotope imaging mass spectrometry (MIMS) with isotope-labeled amino acids directly measured protein replacement rates in hair-cell stereocilia. Bulk stereocilia shaft is remarkably stable: <0.3%/day in adult frog, ~2%/day in adult mouse cochlea. Rapid turnover occurs only at stereocilia tips, not by treadmilling. Actin tracked over 150-day pulse-chase showed <60% replacement even after 5 months in the cochlea.
Relevance for STRC_HL_D modeling
STRC is a tip-link-associated extracellular stereocilin anchored near stereocilia tips. The 14-day estimate used in mrna_lnp_pkpd_integration.py and mrna_lnp_pkpd_integration_v2_ohc_tropism.py is anchored to the bulk shaft regime. The true STRC t½ could range 7–150+ days per this paper’s range, depending on whether STRC turnover tracks tip-specific (faster) or shaft (slower) kinetics. 14 d is order-of-magnitude defensible as an OOM estimate.
NOT an STRC-specific measurement. No primary paper has measured STRC half-life directly.