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Author Notes:

Address correspondence to: Guy M. Benian (pathqb@emory.edu)

We thank Dina Greene and Rachel Stanford for their help in making some of the plasmids.

Subjects:

Research Funding:

G.M.B., H.L., and O.M. gratefully acknowledge support from a Human Frontier Science Program Grant (RGP0044/2012).

E.M. was supported in part by the Robert P. Apkarian Integrated Electron Microscopy Core, which is subsidized by the Emory College of Arts and Sciences and the Emory University School of Medicine.

Additional support was provided by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000454).

EM images were captured with a JEOL JEM-1400 120kV TEM, which is supported by National Institutes of Health Grant S10 RR025679.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • SMALL-ANGLE SCATTERING
  • CAMP-DEPENDENT KINASE
  • CAENORHABDITIS-ELEGANS
  • PROTEIN-KINASE
  • SYNAPTIC FUNCTION
  • UNC-22 GENE
  • DOMAINS
  • OBSCURIN
  • TITIN
  • PHOSPHORYLATION

Twitchin kinase inhibits muscle activity

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Journal Title:

Molecular Biology of the Cell

Volume:

Volume 28, Number 12

Publisher:

, Pages 1591-1600

Type of Work:

Article | Final Publisher PDF

Abstract:

© 2017 Matsunaga et al. Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family's kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no or little activity. Here we address catalytic necessity for the first time, using the prototypic invertebrate representative twitchin (UNC-22) from Caenorhabditis elegans. In in vitro experiments, change of a conserved lysine (K) that is involved in ATP coordination to alanine (A) resulted in elimination of kinase activity without affecting the overall structure of the kinase domain. The same mutation, unc-22(sf21), was generated in the endogenous twitchin gene. The unc-22(sf21) worms have well-organized sarcomeres. However, unc-22(sf21) mutants move faster than wild-type worms and, by optogenetic experiments, contract more. Wild-type nematodes exhibited greater competitive fitness than unc-22(sf21) mutants. Thus the catalytic activity of twitchin kinase has a role in vivo, where it inhibits muscle activity and is likely maintained by selection.

Copyright information:

© 2017 Matsunaga et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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