Sarcomere Formation Occurs by the Assembly of Multiple Latent Protein Complexes

Rui, Yanning; Bai, Jiawei; Perrimon, Norbert

doi:10.1371/journal.pgen.1001208

Cited by 82 publications

(106 citation statements)

References 42 publications

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“…Knockdown of individual sarcomeric proteins can disrupt sarcomere assembly (Rui et al, 2010). We had previously shown that sarcomeric RNAs were downregulated in hoip 1 embryos at St12-13, and that Mhc protein expression was greatly reduced in St16 hoip 1 embryos (Johnson et al, 2013).…”

Section: Tm2 Regulates Sarcomeric Protein Expressionmentioning

confidence: 99%

“…First, the myotube must elongate over several cell diameters to identify and contact the appropriate tendon cells (Schnorrer and Dickson, 2004). Second, the myotube must express a wide range of muscle structural proteins and assemble those proteins into contractile sarcomeres (Rui et al, 2010). Although the mechanisms that regulate myotube precursor specification and muscle structural gene transcription have been characterized in detail (Buckingham and Rigby, 2014;Ciglar and Furlong, 2009), the molecules that coordinate myotube elongation are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…Drosophila somatic muscle is analogous to vertebrate skeletal muscle, and somatic muscle development initiates with the specification of myoblasts known as founder cells, that then fuse with neighboring fusion-competent cells to form nascent, multinucleate myotubes (Chen and Olson, 2004;de Joussineau et al, 2012). The nascent myotubes then elongate, activate muscle structural gene expression, attach to tendons, and assemble sarcomeres to form a functional myofiber (Rui et al, 2010;Schejter and Baylies, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Noncanonical roles for Tropomyosin during myogenesis

et al. 2015

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For skeletal muscle to produce movement, individual myofibers must form stable contacts with tendon cells and then assemble sarcomeres. The myofiber precursor is the nascent myotube, and during myogenesis the myotube completes guided elongation to reach its target tendons. Unlike the well-studied events of myogenesis, such as myoblast specification and myoblast fusion, the molecules that regulate myotube elongation are largely unknown. In Drosophila, hoi polloi (hoip) encodes a highly conserved RNAbinding protein and hoip mutant embryos are largely paralytic due to defects in myotube elongation and sarcomeric protein expression. We used the hoip mutant background as a platform to identify novel regulators of myogenesis, and uncovered surprising developmental functions for the sarcomeric protein Tropomyosin 2 (Tm2). We have identified Hoip-responsive sequences in the coding region of the Tm2 mRNA that are essential for Tm2 protein expression in developing myotubes. Tm2 overexpression rescued the hoip myogenic phenotype by promoting F-actin assembly at the myotube leading edge, by restoring the expression of additional sarcomeric RNAs, and by promoting myoblast fusion. Embryos that lack Tm2 also showed reduced sarcomeric protein expression, and embryos that expressed a gain-of-function Tm2 allele showed both fusion and elongation defects. Tropomyosin therefore dictates fundamental steps of myogenesis prior to regulating contraction in the sarcomere.

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Section: Tm2 Regulates Sarcomeric Protein Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Noncanonical roles for Tropomyosin during myogenesis

et al. 2015

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“…S3I,J). Sarcomere assembly occurs after myotube elongation and myofiber attachment (Rui et al, 2010) and embryos defective for the first round of myoblast fusion do express MHC (Chen and Olson, 2001). Together, these observations demonstrate that muscle morphogenesis is genetically separable from muscle structural expression and prompted us to define a secondary role for Hoip during myogenesis.…”

Section: Somatic and Cardiac Muscle Maturation Is Hoip Dependentmentioning

confidence: 99%

Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi

et al. 2013

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SUMMARYStriated muscle development requires the coordinated expression of genes involved in sarcomere formation and contractility, as well as genes that determine muscle morphology. However, relatively little is known about the molecular mechanisms that control the early stages of muscle morphogenesis. To explore this facet of myogenesis, we performed a genetic screen for regulators of somatic muscle morphology in Drosophila, and identified the putative RNA-binding protein (RBP) Hoi Polloi (Hoip). Hoip is expressed in striated muscle precursors within the muscle lineage and controls two genetically separable events: myotube elongation and sarcomeric protein expression. Myotubes fail to elongate in hoip mutant embryos, even though the known regulators of somatic muscle elongation, target recognition and muscle attachment are expressed normally. In addition, a majority of sarcomeric proteins, including Myosin Heavy Chain (MHC) and Tropomyosin, require Hoip for their expression. A transgenic MHC construct that contains the endogenous MHC promoter and a spliced open reading frame rescues MHC protein expression in hoip embryos, demonstrating the involvement of Hoip in pre-mRNA splicing, but not in transcription, of muscle structural genes. In addition, the human Hoip ortholog NHP2L1 rescues muscle defects in hoip embryos, and knockdown of endogenous nhp2l1 in zebrafish disrupts skeletal muscle development. We conclude that Hoip is a conserved, post-transcriptional regulator of muscle morphogenesis and structural gene expression.

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“…Indeed, the findings from a recent multi-approach study have indicated that the assembly of sarcomeric components into highly ordered structures, including the stereotypic striations, does not occur in a sequential manner, but rather the process is dependent upon the assembly of multiple protein complexes that are preformed (Rui et al, 2010). Knowledge about the mechanisms, which are responsible for maintaining the sarcomeric structures under normal mechanical stress, is however limited.…”

Section: Introductionmentioning

confidence: 99%

Abba is an essential TRIM/RBCC protein for maintaining the integrity of sarcomeric cytoarchitecture

Domsch

Ezzeddine

Nguyen

2013

Journal of Cell Science

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SummaryOrganized sarcomeric striations are an evolutionarily conserved hallmark of functional skeletal muscles. Here, we demonstrate that the Drosophila Abba protein, a member of the TRIM/RBCC superfamily, has a pivotal regulatory role in maintaining proper sarcomeric cytoarchitecture during development and muscle usage. abba mutant embryos initially form muscles, but F-actin and Myosin striations become progressively disrupted when the muscles undergo growth and endure increased contractile forces during larval development. Abnormal Myosin aggregates and myofiber atrophy are also notable in the abba mutants. The larval defects result in compromised muscle function, and hence important morphogenetic events do not occur properly during pupation, leading to lethality. Abba is localized at larval Z-discs, and genetic evidence indicates that abba interacts with a-actinin, kettin/D-titin and mlp84B, genes that encode important Z-disc proteins for stable myofibrillar organization and optimal muscle function. RNAi experiments and ultrastructural analysis reveal that Abba has an additional crucial role in sarcomere maintenance in adult muscles. Abba is required to ensure the integrity and function of Z-discs and M-lines. Rescue experiments further show that Abba function is dependent upon its B-box/coiledcoil domain, NHL repeats and RING finger domain. The importance of these presumed protein-protein interactions and ubiquitin ligaseassociated domains supports our hypothesis that Abba is needed for specific protein complex formation and stabilization at Z-discs and M-lines.

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Sarcomere Formation Occurs by the Assembly of Multiple Latent Protein Complexes

Cited by 82 publications

References 42 publications

Noncanonical roles for Tropomyosin during myogenesis

Noncanonical roles for Tropomyosin during myogenesis

Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi

Abba is an essential TRIM/RBCC protein for maintaining the integrity of sarcomeric cytoarchitecture

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