The genetics and molecular biology of the titin/connectin-like proteins of invertebrates

  • G. M. Benian
  • A. Ayme-Southgate
  • T. L. Tinley
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 138)


A substantial amount of information has been gathered about the structure and function of twitchin/titin-related proteins in the invertebrates. This has been obtained through sequence analysis and the analysis of loss-offunction phenotypes in C. elegans and Drosophila. Nevertheless, a number of fascinating questions remain, including: (i) Why are these invertebrate proteins all of approx. 700–800 kDa? In terms of sarcomeric organization, what is the significance of this size? (ii) Why do three of these proteins consist of a mixture of Ig and Fn domains, whereas UNC-89 contains only Ig domains? This is even more interesting because the structures of Ig and Fn domains are very similar (118). What is the significance of the repeating pattern of groups of Ig and Fn domains (e.g. Fn-Fn-Ig)? (iii) How are twitchin and the synchronous muscle isoform of projectin situated on the surface of thick filaments? That is, do they form polymers or are they located at discrete locations with intervening gaps? (iv) What is the mechanism by which the fundamentally similar projectin isoforms get localized to different sarcomeric locations? (v) If the data on Aplysia twitchin can be extended to the muscles of other invertebrates, what is the mechanism by which twitchin inhibits the rate of relaxation? How does phosphorylation of twitchin relieve this inhibition? (vi) What are the substrates for the protein kinase domains of nematode twitchin and insect projectin? If rMLCs are indeed the substrates, how would and why does this phosphorylation take place for the IFM isoform of projectin, which resides primarily in the I band? If rMLCs are the substrates, given the stoichiometry of approx. 1∶50 for twitchin:myosin, and the likely fixed position of twitchin along the thick filament, how does phosphorylation of just a few rMLCs result in a physiological effect (e.g. inhibition of relaxation)? What is the true activator for the twitchin and projectin kinases? (vii) How does UNC-89 participate in M-line assembly? (viii) What are the biochemical and physiological functions of intestinal brush border twitchin? A number of investigators will enjoy pursuing these and other questions for some time in the future.


Myosin Light Chain Kinase Flight Muscle Thick Filament Body Wall Muscle Protein Kinase Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • G. M. Benian
    • 1
  • A. Ayme-Southgate
    • 2
  • T. L. Tinley
    • 1
  1. 1.Departments of Pathology and Cell BiologyEmory UniversityAtlanta
  2. 2.Department of Molecular BiologyLehigh UniversityBethleham

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