Twitchin kinase inhibits muscle activity
| Autor: | Hang Lu, Olga Mayans, Levi T. Morran, Hyundoo Hwang, McKenna J. Penley, Guy M. Benian, Barbara Franke, Rhys M. Williams, Yohei Matsunaga, Hiroshi Qadota, Hong Yi |
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| Rok vydání: | 2017 |
| Předmět: |
Sarcomeres
0301 basic medicine Mutant Muscle Proteins Biology 03 medical and health sciences In vivo ddc:570 Animals Amino Acid Sequence Phosphorylation Muscle activity Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Kinase Brief Report Lysine Helminth Proteins Cell Biology biology.organism_classification Cell biology 030104 developmental biology Nematode Mutation Calmodulin-Binding Proteins Protein Kinases Muscle Contraction Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Muscles express giant polypeptides with kinase domains, but the in vivo significance of their catalytic activity has been unknown. Analysis of a mutant nematode that expresses the giant protein twitchin with a catalytically inactive kinase indicates that twitchin kinase inhibits muscle activity and is favored by selection. 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. |
| Databáze: | OpenAIRE |
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