Journal article
Differential Actin-regulatory Activities of Tropomodulin1 and Tropomodulin3 with Diverse Tropomyosin and Actin Isoforms
The Journal of biological chemistry, Vol.289(17), pp.11616-11629
04/25/2014
DOI: 10.1074/jbc.M114.555128
PMCID: PMC4002072
PMID: 24644292
Abstract
Background:
Tropomodulins (Tmods) cap pointed ends of actin filaments in a tropomyosin (TM)-dependent manner.
Results:
Tmod1 and Tmod3 similarly cap actin filaments with diverse TM and actin isoforms, but only Tmod3 sequesters β- and γ
cyto
-actin monomers.
Conclusion:
Isoform-specific actin monomer sequestration by Tmod3 may provide a mechanism for actin remodeling in TM-deficient regions of cells.
Significance:
Defining the actin-regulatory activities of Tmods illuminates cytoskeletal dynamics.
Tropomodulins (Tmods) are F-actin pointed end capping proteins that interact with tropomyosins (TMs) and cap TM-coated filaments with higher affinity than TM-free filaments. Here, we tested whether differences in recognition of TM or actin isoforms by Tmod1 and Tmod3 contribute to the distinct cellular functions of these Tmods. We found that Tmod3 bound ∼5-fold more weakly than Tmod1 to α/βTM, TM5b, and TM5NM1. However, surprisingly, Tmod3 was as effective as Tmod1 at capping pointed ends of skeletal muscle α-actin (α
sk
-actin) filaments coated with α/βTM, TM5b, or TM5NM1. Tmod3 only capped TM-coated α
sk
-actin filaments more weakly than Tmod1 in the presence of recombinant αTM2, which is unacetylated at its NH
2
terminus, binds F-actin weakly, and has a disabled Tmod-binding site. Moreover, both Tmod1 and Tmod3 were similarly effective at capping pointed ends of platelet β/cytoplasmic γ (γ
cyto
)-actin filaments coated with TM5NM1. In the absence of TMs, both Tmod1 and Tmod3 had similarly weak abilities to nucleate β/γ
cyto
-actin filament assembly, but only Tmod3 could sequester cytoplasmic β- and γ
cyto
-actin (but not α
sk
-actin) monomers and prevent polymerization under physiological conditions. Thus, differences in TM binding by Tmod1 and Tmod3 do not appear to regulate the abilities of these Tmods to cap TM-α
sk
-actin or TM-β/γ
cyto
-actin pointed ends and, thus, are unlikely to determine selective co-assembly of Tmod, TM, and actin isoforms in different cell types and cytoskeletal structures. The ability of Tmod3 to sequester β- and γ
cyto
-actin (but not α
sk
-actin) monomers in the absence of TMs suggests a novel function for Tmod3 in regulating actin remodeling or turnover in cells.
Details
- Title: Subtitle
- Differential Actin-regulatory Activities of Tropomodulin1 and Tropomodulin3 with Diverse Tropomyosin and Actin Isoforms
- Creators
- Sawako Yamashiro - From theDavid S Gokhin - From theZhenhua Sui - From theSarah E Bergeron - Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242Peter A Rubenstein - Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242Velia M Fowler - From the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.289(17), pp.11616-11629
- DOI
- 10.1074/jbc.M114.555128
- PMID
- 24644292
- PMCID
- PMC4002072
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- R01-HL083464; R01-DC008803 / National Institutes of Health
- Alternative title
- Differential Interactions among Tmods, TMs, and Actins
- Language
- English
- Date published
- 04/25/2014
- Academic Unit
- Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984024523302771
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