A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila

B Naimi; A Harrison; M Cummins; U Nongthomba; S Clark; I Canal; A Ferrus; J C Sparrow

A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila

B Naimi, A Harrison, M Cummins, U Nongthomba, S Clark, I Canal, A Ferrus, J C Sparrow

Research output: Contribution to journal › Article › peer-review

Abstract

A suppressor mutation, D53, of the held-up2 allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up2, including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human -tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

Original language	English
Pages (from-to)	1529-1539
Number of pages	10
Journal	Molecular Biology of the Cell
Volume	12
Issue number	5
Publication status	Published - May 2001

Keywords

FLIGHT-MUSCLE
HYPERTROPHIC CARDIOMYOPATHY
CAENORHABDITIS-ELEGANS
ACTIN-TROPOMYOSIN
ALPHA-TROPOMYOSIN
SKELETAL-MUSCLE
CO-CRYSTALS
MELANOGASTER
GENE
MUTANT

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http://www.molbiolcell.org/cgi/content/abstract/12/5/1529

Cite this

@article{1a009d5f8bf1429c9ef724431e9049c7,

title = "A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila",

abstract = "A suppressor mutation, D53, of the held-up2 allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up2, including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human -tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).",

keywords = "FLIGHT-MUSCLE, HYPERTROPHIC CARDIOMYOPATHY, CAENORHABDITIS-ELEGANS, ACTIN-TROPOMYOSIN, ALPHA-TROPOMYOSIN, SKELETAL-MUSCLE, CO-CRYSTALS, MELANOGASTER, GENE, MUTANT",

author = "B Naimi and A Harrison and M Cummins and U Nongthomba and S Clark and I Canal and A Ferrus and Sparrow, {J C}",

year = "2001",

month = may,

language = "English",

volume = "12",

pages = "1529--1539",

journal = "Molecular Biology of the Cell",

issn = "1059-1524",

publisher = "American Society for Cell Biology",

number = "5",

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TY - JOUR

T1 - A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila

AU - Naimi, B

AU - Harrison, A

AU - Cummins, M

AU - Nongthomba, U

AU - Clark, S

AU - Canal, I

AU - Ferrus, A

AU - Sparrow, J C

PY - 2001/5

Y1 - 2001/5

N2 - A suppressor mutation, D53, of the held-up2 allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up2, including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human -tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

AB - A suppressor mutation, D53, of the held-up2 allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up2, including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human -tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

KW - FLIGHT-MUSCLE

KW - HYPERTROPHIC CARDIOMYOPATHY

KW - CAENORHABDITIS-ELEGANS

KW - ACTIN-TROPOMYOSIN

KW - ALPHA-TROPOMYOSIN

KW - SKELETAL-MUSCLE

KW - CO-CRYSTALS

KW - MELANOGASTER

KW - GENE

KW - MUTANT

M3 - Article

SN - 1059-1524

VL - 12

SP - 1529

EP - 1539

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 5

ER -