JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2054K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kronert, W. A.
Right arrow Articles by Bernstein, S. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kronert, W. A.
Right arrow Articles by Bernstein, S. I.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1999//989 $5.00
The Journal of Cell Biology, Volume 144, Number 5, , 1999 989-1000

Regular Articles

Specific Myosin Heavy Chain Mutations Suppress Troponin I Defects in Drosophila Muscles



William A. Kronert*, Angel Acebes{ddagger}, Alberto Ferrús{ddagger}, and Sanford I. Bernstein*

* Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, California 92182-4614; and {ddagger} Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid 28002, Spain

We show that specific mutations in the head of the thick filament molecule myosin heavy chain prevent a degenerative muscle syndrome resulting from the hdp2 mutation in the thin filament protein troponin I. One mutation deletes eight residues from the actin binding loop of myosin, while a second affects a residue at the base of this loop. Two other mutations affect amino acids near the site of nucleotide entry and exit in the motor domain. We document the degree of phenotypic rescue each suppressor permits and show that other point mutations in myosin, as well as null mutations, fail to suppress the hdp2 phenotype. We discuss mechanisms by which the hdp2 phenotypes are suppressed and conclude that the specific residues we identified in myosin are important in regulating thick and thin filament interactions. This in vivo approach to dissecting the contractile cycle defines novel molecular processes that may be difficult to uncover by biochemical and structural analysis. Our study illustrates how expression of genetic defects are dependent upon genetic background, and therefore could have implications for understanding gene interactions in human disease.

Key Words: Drosophila • muscle • myosin • myofibril • troponin I

Abbreviations used in this paper: Su(hdp2)D; DLM, dorsolongitudinal muscle; MHC, myosin heavy chain; Mhc, myosin heavy chain gene.

We appreciate the help of Dr. Ronald Milligan (The Scripps Research Institute) in preparation of Fig. 2. We thank Drs. Richard Cripps (University of New Mexico), Larry Tobacman (University of Iowa), and Douglas Swank (San Diego State University) for helpful comments on the manuscript.

This research was supported by grants from the Muscular Dystrophy Association and the National Institutes of Health (GM32443) to S.I. Bernstein, and from the Direccion General de Investigacíon Cientifica y Técnica (Spanish Ministry of Culture; PM96-0006) to A. Ferrús.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents