Twitchin Kinase Interacts with MAPKAP Kinase 2 in Caenorhabditis Elegans Striated Muscle

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2015 Apr 9

PMID 25851606

Citations 7

Authors

Yohei Matsunaga

Hiroshi Qadota

Miho Furukawa

Heejoo Helen Choe

Guy M Benian

Affiliations

Soon will be listed here.

Abstract

In Caenorhabditis elegans, twitchin is a giant polypeptide located in muscle A-bands. The protein kinase of twitchin is autoinhibited by 45 residues upstream (NL) and 60 residues downstream (CRD) of the kinase catalytic core. Molecular dynamics simulation on a twitchin fragment revealed that the NL is released by pulling force. However, it is unclear how the CRD is removed. To identify proteins that may remove the CRD, we performed a yeast two-hybrid screen using twitchin kinase as bait. One interactor is MAK-1, C. elegans orthologue of MAPKAP kinase 2. MAPKAP kinase 2 is phosphorylated and activated by p38 MAP kinase. We demonstrate that the CRD of twitchin is important for binding to MAK-1. mak-1 is expressed in nematode body wall muscle, and antibodies to MAK-1 localize between and around Z-disk analogues and to the edge of A-bands. Whereas unc-22 mutants are completely resistant, mak-1 mutants are partially resistant to nicotine. MAK-1 can phosphorylate twitchin NL-Kin-CRD in vitro. Genetic data suggest the involvement of two other mak-1 paralogues and two orthologues of p38 MAP kinase. These results suggest that MAK-1 is an activator of twitchin kinase and that the p38 MAP kinase pathway may be involved in the regulation of twitchin.

Citing Articles

Exploration of the regulatory mechanisms of regeneration, anti-oxidation, anti-aging and the immune response at the post-molt stage of .

Wang M, Ge J, Ma X, Su S, Tian C, Li J Front Physiol. 2022; 13:948511.

PMID: 36237529 PMC: 9552667. DOI: 10.3389/fphys.2022.948511.

Importance of clitellar tissue in the regeneration ability of earthworm Eudrilus eugeniae.

Paul S, Balakrishnan S, Arumugaperumal A, Lathakumari S, Syamala S, Vijayan V Funct Integr Genomics. 2022; 22(4):1-32.

PMID: 35416560 DOI: 10.1007/s10142-022-00849-5.

Conformational changes in twitchin kinase in vivo revealed by FRET imaging of freely moving .

Porto D, Matsunaga Y, Franke B, Williams R, Qadota H, Mayans O Elife. 2021; 10.

PMID: 34569929 PMC: 8523150. DOI: 10.7554/eLife.66862.

Investigating the correlation of muscle function tests and sarcomere organization in C. elegans.

Lesanpezeshki L, Qadota H, Norouzi Darabad M, Kashyap K, Lacerda C, Szewczyk N Skelet Muscle. 2021; 11(1):20.

PMID: 34389048 PMC: 8362255. DOI: 10.1186/s13395-021-00275-4.

NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans.

Rahman M, Hewitt J, Van-Bussel F, Edwards H, Blawzdziewicz J, Szewczyk N Lab Chip. 2018; 18(15):2187-2201.

PMID: 29892747 PMC: 6057834. DOI: 10.1039/c8lc00103k.

References

Moerman D, Benian G, Barstead R, Schriefer L, Waterston R . Identification and intracellular localization of the unc-22 gene product of Caenorhabditis elegans. Genes Dev. 1988; 2(1):93-105. DOI: 10.1101/gad.2.1.93. View

Qadota H, Anraku Y, Botstein D, Ohya Y . Conditional lethality of a yeast strain expressing human RHOA in place of RHO1. Proc Natl Acad Sci U S A. 1994; 91(20):9317-21. PMC: 44803. DOI: 10.1073/pnas.91.20.9317. View

Iyer G, Garrod S, Woods Jr V, Taylor S . Catalytic independent functions of a protein kinase as revealed by a kinase-dead mutant: study of the Lys72His mutant of cAMP-dependent kinase. J Mol Biol. 2005; 351(5):1110-22. DOI: 10.1016/j.jmb.2005.06.011. View

Stokoe D, Engel K, Campbell D, Cohen P, Gaestel M . Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins. FEBS Lett. 1992; 313(3):307-13. DOI: 10.1016/0014-5793(92)81216-9. View

Probst W, Cropper E, Heierhorst J, Hooper S, Jaffe H, Vilim F . cAMP-dependent phosphorylation of Aplysia twitchin may mediate modulation of muscle contractions by neuropeptide cotransmitters. Proc Natl Acad Sci U S A. 1994; 91(18):8487-91. PMC: 44631. DOI: 10.1073/pnas.91.18.8487. View

Qadota H, Mercer K, Miller R, Kaibuchi K, Benian G . Two LIM domain proteins and UNC-96 link UNC-97/pinch to myosin thick filaments in Caenorhabditis elegans muscle. Mol Biol Cell. 2007; 18(11):4317-26. PMC: 2043538. DOI: 10.1091/mbc.e07-03-0278. View

Nonet M, Grundahl K, Meyer B, Rand J . Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell. 1993; 73(7):1291-305. DOI: 10.1016/0092-8674(93)90357-v. View

Meissner B, Warner A, Wong K, Dube N, Lorch A, McKay S . An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans. PLoS Genet. 2009; 5(6):e1000537. PMC: 2694363. DOI: 10.1371/journal.pgen.1000537. View

Bullard B, Linke W, Leonard K . Varieties of elastic protein in invertebrate muscles. J Muscle Res Cell Motil. 2003; 23(5-6):435-47. DOI: 10.1023/a:1023454305437. View

10.

Moerman D, Baillie D . Genetic Organization in CAENORHABDITIS ELEGANS: Fine-Structure Analysis of the unc-22 Gene. Genetics. 1979; 91(1):95-103. PMC: 1213933. DOI: 10.1093/genetics/91.1.95. View

11.

Brenner S . The genetics of Caenorhabditis elegans. Genetics. 1974; 77(1):71-94. PMC: 1213120. DOI: 10.1093/genetics/77.1.71. View

12.

Nakano A, Baines C, Kim S, Pelech S, Downey J, Cohen M . Ischemic preconditioning activates MAPKAPK2 in the isolated rabbit heart: evidence for involvement of p38 MAPK. Circ Res. 2000; 86(2):144-51. DOI: 10.1161/01.res.86.2.144. View

13.

Francis R, Waterston R . Muscle cell attachment in Caenorhabditis elegans. J Cell Biol. 1991; 114(3):465-79. PMC: 2289102. DOI: 10.1083/jcb.114.3.465. View

14.

Lei J, Tang X, Chambers T, Pohl J, Benian G . Protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region. J Biol Chem. 1994; 269(33):21078-85. View

15.

Rogalski T, Williams B, Mullen G, Moerman D . Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan. Genes Dev. 1993; 7(8):1471-84. DOI: 10.1101/gad.7.8.1471. View

16.

Miller R, Qadota H, Landsverk M, Mercer K, Epstein H, Benian G . UNC-98 links an integrin-associated complex to thick filaments in Caenorhabditis elegans muscle. J Cell Biol. 2006; 175(6):853-9. PMC: 2064695. DOI: 10.1083/jcb.200608043. View

17.

Shiroto K, Otani H, Yamamoto F, Huang C, Maulik N, Das D . MK2-/- gene knockout mouse hearts carry anti-apoptotic signal and are resistant to ischemia reperfusion injury. J Mol Cell Cardiol. 2004; 38(1):93-7. DOI: 10.1016/j.yjmcc.2004.10.018. View

18.

Kontrogianni-Konstantopoulos A, Ackermann M, Bowman A, Yap S, Bloch R . Muscle giants: molecular scaffolds in sarcomerogenesis. Physiol Rev. 2009; 89(4):1217-67. PMC: 3076733. DOI: 10.1152/physrev.00017.2009. View

19.

Puchner E, Gaub H . Exploring the conformation-regulated function of titin kinase by mechanical pump and probe experiments with single molecules. Angew Chem Int Ed Engl. 2010; 49(6):1147-50. DOI: 10.1002/anie.200905956. View

20.

Benian G, Tinley T, Tang X, Borodovsky M . The Caenorhabditis elegans gene unc-89, required fpr muscle M-line assembly, encodes a giant modular protein composed of Ig and signal transduction domains. J Cell Biol. 1996; 132(5):835-48. PMC: 2120741. DOI: 10.1083/jcb.132.5.835. View