Requirements of Kettin, a Giant Muscle Protein Highly Conserved in Overall Structure in Evolution, for Normal Muscle Function, Viability, and Flight Activity of <i>Drosophila</i>

Hakeda, Satoko; Endo, Saburo; Saigo, Kaoru

doi:10.1083/jcb.148.1.101

Cited by 70 publications

(75 citation statements)

References 45 publications

(117 reference statements)

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Section: Introductionmentioning

confidence: 80%

“…Importantly, recent molecular genetic studies have shown that kettin is a splice variant of connectin/titin in Drosophila (Machado and Andrew, 2000;Zhang et al, 2000) and crayfish (Fukuzawa et al, 2001). Therefore, the previously reported phenotype of the Drosophila kettin mutants (Hakeda et al, 2000) may be partly due to a defect in the D-titin gene.Based on sequence homology, a gene coding for a kettinlike protein has been found in the nematode Caenorhabditis elegans (Hakeda et al, 2000;Kolmerer et al, 2000). Transcripts of this gene are expressed in various muscle cells, and a Abbreviations used: GST, glutathione S-transferase; Ig, immunoglobulin-like; RNAi, RNA interference.…”

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confidence: 80%

“…Kettin is one of the first proteins to colocalize with actin during the early stages of myofibrillogenesis (Ayme-Southgate et al, 2004), and genetic analysis has shown that it is essential for myofibril assembly in the fruit fly (Hakeda et al, 2000). The sequence of kettin contains 35 immunoglobulin-like (Ig) repeats separated by short linker sequences (Hakeda et al, 2000;Kolmerer et al, 2000) and is related to the connectin/titin family of giant elastic proteins (Maruyama, 1997;Gautel et al, 1999;Gregorio et al, 1999;Maruyama and Kimura, 2000;Granzier et al, 2002). However, kettin does not have fibronectin-like, elastic PEVK, or kinase domains, and seems to be a uniquely evolved member of the connectin/titin family of proteins.…”

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confidence: 99%

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Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

Ono

Mohri

et al. 2006

MBoC

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Kettin is a large actin-binding protein with immunoglobulin-like (Ig) repeats, which is associated with the thin filaments in arthropod muscles. Here, we report identification and functional characterization of kettin in the nematode Caenorhabditis elegans. We found that one of the monoclonal antibodies that were raised against C. elegans muscle proteins specifically reacts with kettin (Ce-kettin). We determined the entire cDNA sequence of Ce-kettin that encodes a protein of 472 kDa with 31 Ig repeats. Arthropod kettins are splice variants of much larger connectin/titin-related proteins. However, the gene for Ce-kettin is independent of other connectin/titin-related genes. Ce-kettin localizes to the thin filaments near the dense bodies in both striated and nonstriated muscles. The C-terminal four Ig repeats and the adjacent non-Ig region synergistically bind to actin filaments in vitro. RNA interference of Ce-kettin caused weak disorganization of the actin filaments in body wall muscle. This phenotype was suppressed by inhibiting muscle contraction by a myosin mutation, but it was enhanced by tetramisole-induced hypercontraction. Furthermore, Ce-kettin was involved in organizing the cytoplasmic portion of the dense bodies in cooperation with ␣-actinin. These results suggest that kettin is an important regulator of myofibrillar organization and provides mechanical stability to the myofibrils during contraction. INTRODUCTIONIn muscle cells, the actin cytoskeleton is highly differentiated to form the myofibrils that are specialized for producing contractile forces. In addition to actin and myosin as the essential contractile components, regulatory components for the contractile activity are integrated into the structure (Squire, 1997). Despite the fact that many myofibrillar components have been identified, little is known about how these components functionally interact to assemble and maintain the myofibrils in living cells (Littlefield and Fowler, 1998;Gregorio and Antin, 2000;Clark et al., 2002). In particular, the assembly process of actin filaments is complex. During development, actin-monomer binding proteins, including profilin, and actin depolymerizing factor/cofilin regulate actin filament dynamics (Obinata, 1993;Obinata et al., 1997; Ono, 2003a,b). However, in mature myofibrils, these proteins are no longer major components of the thin filaments, and filament binding proteins, such as tropomyosin and ␣-actinin, and end-capping proteins, such as CapZ and tropomodulin, become the major actin-associated proteins. However, the list of actin binding proteins in muscle is still growing and cellular functions of many of these proteins are not clearly understood.Kettin is a large protein of 500-700 kDa found in the Z-discs and the I-bands of arthropod muscles (Bullard et al., 2000;Bullard et al., 2002Bullard et al., , 2006. Kettin directly binds to actin filaments with high-affinity (Lakey et al., 1993;Maki et al., 1995;van Straaten et al., 1999). Proteolytic removal of kettin by calpain from the Z-discs causes ...

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Section: Introductionmentioning

confidence: 80%

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confidence: 80%

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confidence: 99%

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Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

Ono

Mohri

et al. 2006

MBoC

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“…The elastic filaments projectin and kettin (45) probably supply the radial force for lattice compression and if they bind tangentially to the end of the thick filament could also supply the necessary torque for myosin filament twist. This could explain the loss of flight in heterozygous kettin mutants in Drosophila (46).…”

Section: Discussionmentioning

confidence: 99%

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

Edwards

Irving

Baumann

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

108

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Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin's steric blocking of myosin-actin binding. This enables subsequent force production, with crossbridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection.S tretch activation is a striking example of mechanical signal transduction, in which stretching a partially activated muscle yields, after a delay, greater activation. It is observed to varying degrees in all striated muscles, is prominent in vertebrate cardiac muscle where it may underlie the Frank-Starling relationship (1), and is essential to flight in multiple orders of insects, which together comprise ∼75% of insect species (2) and fully half of all animal taxa (3). Since stretch activation was first reported by Pringle (4), a great deal has been learned about how muscular contraction is driven by cyclic myosin-actin interactions (5) which, in vertebrate skeletal muscles, are controlled by calcium's effect on the steric blocking action of troponin-tropomyosin (6). However, even atomic resolution models of myosin-actin (7) and the troponin complex (8, 9) fail to shed any light on the mechanism of activation by stretch. The central question of stretch activation remains: How does mechanical stress convert to myosinactin activation while the requisite [Ca 2þ ] stays constant?Recently we observed cross-bridges between thick (mainly myosin) filaments and thin (mainly actin-troponin-tropomyosin) filaments at the level of the troponin (10). These myosin-troponin connections, referred to here simply as troponin bridges, comprised about 15% of all cross-bridges identified in an insect flight muscle (IFM) quick frozen during an isometric contraction. Troponin bridges represent a newly recognized class of crossbridges, distinct from the "traditional" force-generating myosin cross-bridges that bind to actin target zones halfway between troponins in IFM (10, 11). The direct observation of troponin bridges revived a previously speculative mechanism for stretch activation (12), in which troponin bridges serve as the agent of mechanica...

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“…During Drosophila embryogenesis trh is expressed in a cell population that migrates from the ventral ectoderm dorsally to become either glands (corpora cardiaca, prothoracic gland) in anterior segments, or tracheae in segments T2 through A8 (25,26). Also absent from T1 EW (Table S2) was a wing-specific isoform of salimus (sls), a gene involved in muscle development and attachment (27)(28)(29) that in Drosophila is coexpressed with trh in ventral-origin cells. Another tracheal morphogenesis gene, forked (f) (30), involved in formation of mechanosensory wing bristles (31), was among the wing-specific genes missing from T1 EW.…”

Section: Insights About Wing Origins and Functionalization From T1 Ecmentioning

confidence: 99%

Origin and diversification of wings: Insights from a neopteran insect

Medved

Marden

Fescemyer

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Winged insects underwent an unparalleled evolutionary radiation, but mechanisms underlying the origin and diversification of wings in basal insects are sparsely known compared with more derived holometabolous insects. In the neopteran species Oncopeltus fasciatus, we manipulated wing specification genes and used RNA-seq to obtain both functional and genomic perspectives. Combined with previous studies, our results suggest the following key steps in wing origin and diversification. First, a set of dorsally derived outgrowths evolved along a number of body segments including the first thoracic segment (T1). Homeotic genes were subsequently co-opted to suppress growth of some dorsal flaps in the thorax and abdomen. In T1 this suppression was accomplished by Sex combs reduced, that when experimentally removed, results in an ectopic T1 flap similar to prothoracic winglets present in fossil hemipteroids and other early insects. Global geneexpression differences in ectopic T1 vs. T2/T3 wings suggest that the transition from flaps to wings required ventrally originating cells, homologous with those in ancestral arthropod gill flaps/epipods, to migrate dorsally and fuse with the dorsal flap tissue thereby bringing new functional gene networks; these presumably enabled the T2/T3 wing's increased size and functionality. Third, "fused" wings became both the wing blade and surrounding regions of the dorsal thorax cuticle, providing tissue for subsequent modifications including wing folding and the fit of folded wings. Finally, Ultrabithorax was co-opted to uncouple the morphology of T2 and T3 wings and to act as a general modifier of hindwings, which in turn governed the subsequent diversification of lineage-specific wing forms.wing origins | Sex combs reduced | Ultrabithorax | RNA-seq | vestigial S ome 350 million years ago, the development of insect wings was a seminal event in the evolution of insect body design (1, 2). The ability to fly was critical to insects becoming the most diverse and abundant animal group, and the origin of such novelty has been a focus of intense scientific inquiry for more than a century (3, 4). More recently, through studies of genetic model systems such as Drosophila, the mechanisms of wing morphogenesis have been elucidated (5-12). Still lacking however is a comprehensive understanding of transitional steps connecting the morphology of structures observed in the fossil record with that of the modern-day insects, including wing origins and subsequent diversification.The initial stages of insect wing evolution are missing from the fossil record and it is therefore necessary to use indirect evidence from fossils that postdate the origin and initial radiation of pterygotes (2). Larvae of many of those taxa featured dorsally positioned outgrowths on each of the thoracic and abdominal segments (2, 13), apparently serial homologs (i.e., similar structures likely arising from a common set of developmental mechanisms). Diverse lineages independently lost those dorsal appendages on the abdomen while un...

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Requirements of Kettin, a Giant Muscle Protein Highly Conserved in Overall Structure in Evolution, for Normal Muscle Function, Viability, and Flight Activity of Drosophila

Cited by 70 publications

References 45 publications

Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

Origin and diversification of wings: Insights from a neopteran insect

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