Capping Protein Dissociation Half-Life

P0 data. Capping protein (CP, the α/β heterodimer aka CapZ in muscle) binds the actin barbed end with a dissociation half-time of 30 minutes [Pollard 2016, p.4 §10].

Verbatim values

QuantityValueCitation
Architectureα/β heterodimer[Pollard 2016, p.4]
Cellular concentrationlow micromolar[Pollard 2016, p.4]
Time to cap a free barbed endseconds (at cellular [CP])[Pollard 2016, p.4]
t½ for dissociation from barbed end30 min[Pollard 2016, p.4]

Implied k_off ≈ ln(2) / (30 × 60 s) = 3.85 × 10⁻⁴ s⁻¹.

What the 30-min off-rate implies

  • A capped barbed end is, on the timescale of most cellular actin dynamics (seconds to minutes), effectively permanent.
  • For barbed ends to be re-opened on a faster timescale, cells use regulated uncapping:
    • Polyphosphoinositides (PIP₂) — sterically block CP rebinding but do not eject CP from a filament end [Pollard 2016, p.4].
    • V-1 / myotrophin — sequester free CP in the cytoplasm.
    • CARMIL — allosteric weakener that lets CP bind weakly and slow elongation rather than fully cap [Pollard 2016, p.4 (Edwards 2014)].

Relevance to STRC

  1. Stereocilia barbed ends (tips) are NOT capped by CP — they are kept polymerization-competent (espin/EPS8/whirlin family at the tip). The CP 30-min off-rate is therefore the right comparison number to argue why stereocilia tip elongation requires constant active uncapping or local CP exclusion.
  2. Stereocilia pointed ends (bases) are capped by tropomodulin, not by CP — see [[Tropomodulin Pointed End Cap Mechanism]]. The tropomodulin off-rate is slower still and stabilized by tropomyosin.
  3. h09 hydrogel models that introduce synthetic actin-binding sequences should treat any region that mimics CP’s barbed-end binding as effectively irreversible on cellular timescales — relevant for thinking about therapeutic ototopical residence times (hours to days vs cellular seconds).

Anti-fabrication notes

  • Pollard 2016 gives the 30-min half-time and a verbal “low micromolar” concentration; the exact cellular [CP] is not stated in this review. For a specific concentration, retrieve Schafer et al. 1996 J Cell Biol or Cooper & Sept 2008 Int Rev Cell Mol Biol.
  • The k_off conversion above (3.85 × 10⁻⁴ s⁻¹) is a derived number, not stated in Pollard 2016. Cite as derived if used.

Connections