Tropomodulins and Leiomodins: Actin Pointed End Caps and Nucleators in Muscles

Biophysical Journal
V M Fowler, Roberto Dominguez

Abstract

Cytoskeletal structures characterized by actin filaments with uniform lengths, including the thin filaments of striated muscles and the spectrin-based membrane skeleton, use barbed and pointed-end capping proteins to control subunit addition/dissociation at filament ends. While several proteins cap the barbed end, tropomodulins (Tmods), a family of four closely related isoforms in vertebrates, are the only proteins known to specifically cap the pointed end. Tmods are ∼350 amino acids in length, and comprise alternating tropomyosin- and actin-binding sites (TMBS1, ABS1, TMBS2, and ABS2). Leiomodins (Lmods) are related in sequence to Tmods, but display important differences, including most notably the lack of TMBS2 and the presence of a C-terminal extension featuring a proline-rich domain and an actin-binding WASP-Homology 2 domain. The Lmod subfamily comprises three somewhat divergent isoforms expressed predominantly in muscle cells. Biochemically, Lmods differ from Tmods, acting as powerful nucleators of actin polymerization, not capping proteins. Structurally, Lmods and Tmods display crucial differences that correlate well with their different biochemical activities. Physiologically, loss of Lmods in striated muscle results in...Continue Reading

Citations

Oct 17, 2017·Journal of Cell Science·Klemens RottnerEugen Kerkhoff
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tongbin WuJu Chen
Jul 18, 2019·Journal of Muscle Research and Cell Motility·Sawako Yamashiro, Naoki Watanabe
Sep 9, 2020·PLoS Biology·Dmitri TolkatchevAlla S Kostyukova
Nov 16, 2018·Biophysics Reviews·Justin Parreno, Velia M Fowler
Mar 21, 2019·Journal of Cell Science·Tiina ViitaMaria K Vartiainen
Jan 4, 2020·PloS One·Lei Mi-MiCarol C Gregorio
Feb 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Roberto Dominguez
Jul 5, 2019·Journal of Muscle Research and Cell Motility·Joanna Moraczewska
Nov 12, 2020·Biology·Jaya Aseervatham
Mar 21, 2021·Communications Biology·Mert ColpanCarol C Gregorio
Mar 20, 2021·The Journal of General Physiology·Christopher Solís, R John Solaro
Aug 14, 2018·Journal of Molecular and Cellular Cardiology·Christopher T PappasCarol C Gregorio
May 26, 2021·Current Biology : CB·Arit Ghosh, Velia M Fowler
Jul 17, 2021·Trends in Cell Biology·Jessika IwanskiMert Colpan
Jul 18, 2021·The FEBS Journal·Dmitri TolkatchevAlla S Kostyukova

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