CAP2 is a regulator of actin pointed end dynamics and myofibrillogenesis in cardiac muscle

Commun Biol. 2021 Mar 19;4(1):365. doi: 10.1038/s42003-021-01893-w.

Abstract

The precise assembly of actin-based thin filaments is crucial for muscle contraction. Dysregulation of actin dynamics at thin filament pointed ends results in skeletal and cardiac myopathies. Here, we discovered adenylyl cyclase-associated protein 2 (CAP2) as a unique component of thin filament pointed ends in cardiac muscle. CAP2 has critical functions in cardiomyocytes as it depolymerizes and inhibits actin incorporation into thin filaments. Strikingly distinct from other pointed-end proteins, CAP2's function is not enhanced but inhibited by tropomyosin and it does not directly control thin filament lengths. Furthermore, CAP2 plays an essential role in cardiomyocyte maturation by modulating pre-sarcomeric actin assembly and regulating α-actin composition in mature thin filaments. Identification of CAP2's multifunctional roles provides missing links in our understanding of how thin filament architecture is regulated in striated muscle and it reveals there are additional factors, beyond Tmod1 and Lmod2, that modulate actin dynamics at thin filament pointed ends.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism*
  • Age Factors
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chick Embryo
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Development*
  • Myocytes, Cardiac / metabolism*
  • Myofibrils / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Tropomyosin / metabolism

Substances

  • Actins
  • Cap2 protein, rat
  • Carrier Proteins
  • Membrane Proteins
  • Tropomyosin
  • alpha-smooth muscle actin, mouse
  • cyclase-associated protein 2, mouse