Three New Isoforms of Caenorhabditis elegans UNC-89 Containing MLCK-like Protein Kinase Domains

Small, Tracey M.; Gernert, Kim M.; Flaherty, Denise B.; Mercer, Kristina B.; Borodovsky, Mark; Benian, Guy M.

doi:10.1016/j.jmb.2004.07.006

Cited by 72 publications

(104 citation statements)

References 35 publications

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“…ketn-1 (RNAi) caused disorganization of actin filaments in muscle. This phenotype is different from the defects in regulation of muscle contraction in the mutants of unc-22 coding for twitchin (Benian et al, 1993) and the defects in M-line assembly in the mutants of unc-89 coding for UNC-89, a protein similar to obscurin (Benian et al, 1996;Small et al, 2004). Therefore, the RNAi phenotype strongly suggests that Cekettin has specific function in assembly and/or maintenance of actin filaments in muscle.…”

Section: Discussionmentioning

confidence: 88%

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: Discussionmentioning

confidence: 88%

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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“…These included the Caenorhabditis elegans UNC89, which encodes a very large protein required for myofibril organization in C. elegans. This protein contains a myosin light-chain kinase domain (Benian et al 1996;Small et al 2004).…”

Section: Resultsmentioning

confidence: 99%

The shavenoid Gene of Drosophila Encodes a Novel Actin Cytoskeleton Interacting Protein That Promotes Wing Hair Morphogenesis

Ren

He²,

Stone

et al. 2006

Genetics

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The simple cellular composition and array of distally pointing hairs has made the Drosophila wing a favored system for studying planar polarity and the coordination of cellular-and tissue-level morphogenesis. The developing hairs are filled with F-actin and microtubules and the activity of these cytoskeletons is important for hair morphogenesis. On the basis of mutant phenotypes several genes have been identified as playing a key role in stimulating hair formation. Mutations in shavenoid (sha) (also known as kojak) result in a delay in hair morphogenesis and in some cells forming no hair and others several small hairs. We report here the molecular identification and characterization of the sha gene and protein. sha encodes a large novel protein that has homologs in other insects, but not in more distantly related organisms. The Sha protein accumulated in growing hairs and bristles in a pattern that suggested that it could directly interact with the actin cytoskeleton. Consistent with this mechanism of action we found that Sha and actin co-immunopreciptated from wing disc cells. The morphogenesis of the hair involves temporal control by sha and spatial control by the genes of the frizzled planar polarity pathway. We found a strong genetic interaction between mutations in these genes consistent with their having a close but parallel functional relationship.

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“…The single UNC-89 gene contains three promoters, is highly alternatively spliced, providing complexity to this family of polypeptides, and generates various isoforms consisting of structural domains and signaling motifs ( Fig. 1) (Benian et al 1996;Ferrara et al 2005;Qadota et al 2008a;Small et al 2004). Similar to mammalian obscurins, there are several UNC-89 isoforms, ranging in size from ∼900 to 156 kDa.…”

Section: Complexity Of the Domain Architectures Of Obscurinsmentioning

confidence: 99%

Obscure functions: the location–function relationship of obscurins

2017

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The obscurin family of polypeptides is essential for normal striated muscle function and contributes to the pathogenesis of fatal diseases, including cardiomyopathies and cancers. The single mammalian obscurin gene, OBSCN, gives rise to giant (∼800 kDa) and smaller (∼40-500 kDa) proteins that are composed of tandem adhesion and signaling motifs. Mammalian obscurin proteins are expressed in a variety of cell types, including striated muscles, and localize to distinct subcellular compartments where they contribute to diverse cellular processes. Obscurin homologs in Caenorhabditis elegans and Drosophila possess a similar domain architecture and are also expressed in striated muscles. The long sought after question, "what does obscurin do?" is complex and cannot be addressed without taking into consideration the subcellular distribution of these proteins and local isoform concentration. Herein, we present an overview of the functions of obscurins and begin to define the intricate relationship between their subcellular distributions and functions in striated muscles.

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Three New Isoforms of Caenorhabditis elegans UNC-89 Containing MLCK-like Protein Kinase Domains

Cited by 72 publications

References 35 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

The shavenoid Gene of Drosophila Encodes a Novel Actin Cytoskeleton Interacting Protein That Promotes Wing Hair Morphogenesis

Obscure functions: the location–function relationship of obscurins

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