Mammalian tropomodulins nucleate actin polymerization via their actin monomer binding and filament pointed end-capping activities.

The Journal of Biological Chemistry
Sawako YamashiroV M Fowler

Abstract

Many actin-binding proteins have been shown to possess multiple activities to regulate filament dynamics. Tropomodulins (Tmod1-4) are a conserved family of actin filament pointed end-capping proteins. Our previous work has demonstrated that Tmod3 binds to monomeric actin in addition to capping pointed ends. Here, we show a novel actin-nucleating activity in mammalian Tmods. Comparison of Tmod isoforms revealed that Tmod1-3 but not Tmod4 nucleate actin filament assembly. All Tmods bind to monomeric actin, and Tmod3 forms a 1:1 complex with actin. By truncation and mutagenesis studies, we demonstrated that the second α-helix in the N-terminal domain of Tmod3 is essential for actin monomer binding. Chemical cross-linking and LC-MS/MS further indicated that residues in this second α-helix interact with actin subdomain 2, whereas Tmod3 N-terminal domain peptides distal to this α-helix interact with actin subdomain 1. Mutagenesis of Leu-73 to Asp, which disrupts the second α-helix of Tmod3, decreases both its actin monomer-binding and -nucleating activities. On the other hand, point mutations of residues in the C-terminal leucine-rich repeat domain of Tmod3 (Lys-317 in the fifth leucine-rich repeat β-sheet and Lys-344 or Arg-345/Arg-...Continue Reading

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Citations

Nov 15, 2011·American Journal of Physiology. Cell Physiology·David S GokhinVelia M Fowler
Oct 21, 2011·Journal of Biomedicine & Biotechnology·David S Gokhin, Velia M Fowler
Jul 26, 2014·Science·Jampani Nageswara RaoRoberto Dominguez
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Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tongbin WuJu Chen
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Mar 20, 2014·The Journal of Biological Chemistry·Sawako YamashiroVelia M Fowler
Nov 16, 2018·Biophysics Reviews·Justin Parreno, Velia M Fowler
Oct 26, 2018·Frontiers in Molecular Neuroscience·Kevin T GrayAlla S Kostyukova
Aug 14, 2018·Journal of Molecular and Cellular Cardiology·Christopher T PappasCarol C Gregorio
May 8, 2021·Frontiers in Endocrinology·Man Mohan ShresthaWeiping Han

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