A cis-Regulatory Mutation in Troponin-I of Drosophila Reveals the Importance of Proper Stoichiometry of Structural Proteins During Muscle Assembly

Firdaus, Hena and Mohan, Jayaram and Naz, Sarwat and Arathi, Prabhashankar and Ramesh, Saraf R and Nongthomba, Upendra (2015) A cis-Regulatory Mutation in Troponin-I of Drosophila Reveals the Importance of Proper Stoichiometry of Structural Proteins During Muscle Assembly. In: GENETICS, 200 (1). 149-U322.

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Abstract

Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.

Item Type:	Journal Article
Publication:	GENETICS
Publisher:	GENETICS SOCIETY AMERICA
Additional Information:	Copy right for this article belongs to the GENETICS SOCIETY AMERICA, 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
Keywords:	Drosophila; flight muscles; troponin; muscle hypercontraction; protein stoichiometry
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	15 Jun 2015 05:31
Last Modified:	15 Jun 2015 05:31
URI:	http://eprints.iisc.ac.in/id/eprint/51646

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