Troponin I and Tropomyosin regulate chromosomal stability and cell polarity

Sahota, Virender K.; Grau, Benjamin; Mansilla, Alicia; Ferrús, Alberto

doi:10.1242/jcs.050880

Cited by 43 publications

(52 citation statements)

References 52 publications

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“…In the absence of TnI, an inhibitory component within the troponin-complex proteins, the unregulated actomyosin interactions cause hypercontraction of the IFMs and TDT during early myofibrillogenesis (Nongthomba et al 2004). Using the UH3-Gal4 line, we attempted to rescue the hdp 3 allele with a nonflight muscle isoform of TnI, TnI-L9 (embryonic isoform) (Sahota et al 2009), to study the importance of isoform switching. Since, the driver UH3-Gal4 and the mutant allele hdp 3 are located on the X chromosome, we first recombined both alleles into a single chromosome and confirmed the muscle phenotype (figure 4b), which retained the hdp 3 phenotype.…”

Section: Embryonic Isoform Of Tni Rescues Myofibril Structure Of Nullmentioning

confidence: 99%

Roles of the troponin isoforms during indirect flight muscle development in Drosophila

Singh

Kumar

Ramachandra

et al. 2014

J Genet

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Troponin proteins in cooperative interaction with tropomyosin are responsible for controlling the contraction of the striated muscles in response to changes in the intracellular calcium concentration. Contractility of the muscle is determined by the constituent protein isoforms, and the isoforms can switch over from one form to another depending on physiological demands and pathological conditions. In Drosophila, a majority of the myofibrillar proteins in the indirect flight muscles (IFMs) undergo post-transcriptional and post-translational isoform changes during pupal to adult metamorphosis to meet the high energy and mechanical demands of flight. Using a newly generated Gal4 strain (UH3-Gal4) which is expressed exclusively in the IFMs, during later stages of development, we have looked at the developmental and functional importance of each of the troponin subunits (troponin-I, troponin-T and troponin-C) and their isoforms. We show that all the troponin subunits are required for normal myofibril assembly and flight, except for the troponin-C isoform 1 (TnC1). Moreover, rescue experiments conducted with troponin-I embryonic isoform in the IFMs, where flies were rendered flightless, show developmental and functional differences of TnI isoforms and importance of maintaining the right isoform.[Singh S. H., Kumar P., Ramachandra N. B. and Nongthomba U. 2014 Roles of the troponin isoforms during indirect flight muscle development in Drosophila. J. Genet. 93, [379][380][381][382][383][384][385][386][387][388]

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Section: Embryonic Isoform Of Tni Rescues Myofibril Structure Of Nullmentioning

confidence: 99%

Roles of the troponin isoforms during indirect flight muscle development in Drosophila

Singh

Kumar

Ramachandra

et al. 2014

J Genet

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“…As TnT3, TnT1, and TnT2 exhibit a classical LZD (Vinson et al ., 1989), TnT1 and TnT2 may have a nuclear function similar to that described for TnT3 in the present study. TnI has been reported in the nucleus of Drosophila nonmuscle cells (Sahota et al ., 2009) and TnI and TnT in rat and human cardiomyocytes (Asumda & Chase, 2012); however, their function in these locations is largely unknown. We consistently demonstrated that the nonmyofilament‐associated fast skeletal muscle TnT3 enters the nucleus through a COOH‐terminus nuclear localization sequence (NLS), KLKRQK (Zhang et al ., 2013a).…”

Section: Discussionmentioning

confidence: 99%

Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1 , and enhances skeletal muscle force in aging sedentary mice

et al. 2016

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SummaryLoss of strength in human and animal models of aging can be partially attributed to a well‐recognized decrease in muscle mass; however, starting at middle‐age, the normalized force (force/muscle cross‐sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca2+ channel α1 subunit (Cav1.1) with aging leads to excitation–contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full‐length TnT3 (FL‐TnT3) and its carboxyl‐terminal (CT‐TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA‐410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice.

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“…However, recently, expression of troponin in mouse vascular smooth muscle has been reported (Moran et al, 2008), although its function is still unclear. Furthermore, TNI is involved in the regulation of chromosomal stability and cell polarity in early Drosophila embryos (Sahota et al, 2009). Thus, additional cell-biological and genetic investigation on troponin in non-striated muscle and non-muscle cells might reveal unknown functions of the troponin complex or individual troponin components.…”

Section: (Rnai)mentioning

confidence: 99%

Troponin I controls ovulatory contraction of non-striated actomyosin networks in the C. elegans somatic gonad

Obinata

Ono

2010

Journal of Cell Science

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SummaryThe myoepithelial sheath of the Caenorhabditis elegans somatic gonad has non-striated actomyosin networks that provide contractile forces during ovulation, a process in which a mature oocyte is expelled from the ovary. Troponin T and troponin C are known regulators of contraction of the myoepithelial sheath. These are two of the three components of the troponin complex that is generally considered as a striated-muscle-specific regulator of actomyosin contraction. Here, we report identification of troponin I as the third component of the troponin complex that regulates ovulatory contraction of the myoepithelial sheath. C. elegans has four genes encoding troponin-I isoforms. We found that tni-1 and unc-27 (also known as tni-2) encode two major troponin-I isoforms in the myoepithelial sheath. Combination of RNA interference and mutation of tni-1 and unc-27 resulted in loss of the troponin-I protein in the gonad and caused sterility due to defective contraction of the myoepithelial sheath. Troponin-I-depleted gonads were hypercontracted, which is consistent with the function of troponin I as an inhibitor of actomyosin contraction. Troponin I was associated with nonstriated actin networks in a tropomyosin-dependent manner. Our results demonstrate that troponin I regulates contraction of nonstriated actomyosin networks and is an essential cytoskeletal component of the C. elegans reproductive system.

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Troponin I and Tropomyosin regulate chromosomal stability and cell polarity

Abstract: doi:10.1242/jcs.05088

Cited by 43 publications

References 52 publications

Roles of the troponin isoforms during indirect flight muscle development in Drosophila

Roles of the troponin isoforms during indirect flight muscle development in Drosophila

Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1 , and enhances skeletal muscle force in aging sedentary mice

Troponin I controls ovulatory contraction of non-striated actomyosin networks in the C. elegans somatic gonad

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