Two Caenorhabditis elegans Actin Depolymerizing Factor/Cofilin Proteins, Encoded by the unc-60 Gene, Differentially Regulate Actin Filament Dynamics

Ono, Shoichiro; Benian, Guy M.

doi:10.1074/jbc.273.6.3778

Cited by 91 publications

(127 citation statements)

References 38 publications

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“…However, ADF is more sensitive to changes in pH than cofilin 61 . In addition, in the mouse and C. elegans, the non-muscle isoforms cofilin 1 and ADF are more efficient at depolymerizing F-actin in vitro than the muscle isoform of cofilin 62,63 . These findings suggest that specific cofilin isoforms may be crucial to the changes in cell shape and migration that occur during different stages of embryonic development and morphogenesis.…”

Section: Box 2 Linking Cofilin To Drosophila Melanogaster Morphogenesismentioning

confidence: 98%

The cofilin pathway in breast cancer invasion and metastasis

Wang¹,

2007

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Recent evidence indicates that metastatic capacity is an inherent feature of breast tumours and not a rare, late acquired event. This has led to new models of metastasis. The interpretation of expression-profiling data in the context of these new models has identified the cofilin pathway as a major determinant of metastasis. Recent studies indicate that the overall activity of the cofilin pathway, and not that of any single gene within the pathway, determines the invasive and metastatic phenotype of tumour cells. These results predict that inhibitors directed at the output of the cofilin pathway will have therapeutic benefit in combating metastasis.Tumour cell motility is the hallmark of invasion and an essential step in metastasis 1,2 . The identification of molecular pathways that contribute to tumour cell motility and invasion is essential for understanding how motility is initiated in tumour cells and how the tumour microenvironment contributes to cell migration. The identification of the molecular pathways of tumour cell invasion will provide new diagnostic approaches and targets for the treatment of metastatic cancer. Recent studies using new technologies, including highdensity microarray-based expression profiling, intravital imaging and the collection of invasive tumour cells from live tumours, have started to extend the traditional model of metastasis and supply new diagnostic and therapeutic markers of metastatic disease.According to the traditional model of metastasis, metastases result from a process similar to Darwinian evolution whereby natural selection works on individual tumour cells to select © 2007 Nature Publishing Group Correspondence to: J.C. Condeeli@aecom.yu.edu. Competing interests statementThe authors declare no competing financial interests. for stable genetic changes. The cells so selected are very rare, and the metastatic cells that arise from this progressive selection of stable genetic mutations within the primary tumour cause metastasis late in tumour progression 3 . However, studies of mammary tumours in mice [4][5][6][7] , expression profiling of both whole human breast tumours 8,9 and the invasive subpopulation of tumour cells isolated from rat and mouse mammary tumours [10][11][12] suggest that the metastatic ability of breast tumours is encoded throughout the bulk of the primary tumour, involves transient changes in gene expression and is acquired at much earlier stages of tumour progression than postulated by the traditional model. These results suggest that a Darwinian-like evolution is accompanied by, and may contribute to, microenvironmentinduced transient changes in gene expression that support the invasive and metastatic phenotype. These results have led to new models where the microenvironment initiates the expression of genes that induce cell motility, invasion and metastasis 11,13 . In the 'tumour microenvironment invasion model' it is proposed that oncogenic mutations in tumour cells lead to microenvironments that are potentially encoded throughout the b...

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Section: Box 2 Linking Cofilin To Drosophila Melanogaster Morphogenesismentioning

confidence: 98%

The cofilin pathway in breast cancer invasion and metastasis

Wang¹,

2007

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“…UNC-60B is an I-band protein, which controls the turnover of actin filaments by accelerating the rate of depolymerization at the pointed ends and by severing actin filaments 22,14 . Fluorescence microscopy of contracting body wall muscles of C. elegans revealed that GFP-UNC-60B was indeed abnormally accumulated along I-bands in the contracted state in the dbn-1 (ok925) mutant and in dbn-1 (RNAi) worms compared with the regular pattern in wild-type worms ( Fig.…”

Section: Nature Communications | Doimentioning

confidence: 99%

“…The bestdescribed protein of the first class in C. elegans is the ADF/ cofilin homologue UNC-60B. Inside the sarcomere, this protein is localized to the I-band and enhances actin-filament turnover by accelerating the rate of depolymerization at the pointed ends and by severing filaments 22,14 . Mutations in the unc-60B gene result in the formation of highly disorganized sarcomeres and the appearance of large aggregates of actin at the lateral ends of bodywall muscle cells 23 .…”

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confidence: 99%

Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

et al. 2015

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Actin filament organization and stability in the sarcomeres of muscle cells are critical for force generation. Here we identify and functionally characterize a Caenorhabditis elegans drebrin-like protein DBN-1 as a novel constituent of the muscle contraction machinery. In vitro, DBN-1 exhibits actin filament binding and bundling activity. In vivo, DBN-1 is expressed in body wall muscles of C. elegans. During the muscle contraction cycle, DBN-1 alternates location between myosin-and actin-rich regions of the sarcomere. In contracted muscle, DBN-1 is accumulated at I-bands where it likely regulates proper spacing of a-actinin and tropomyosin and protects actin filaments from the interaction with ADF/cofilin. DBN-1 loss of function results in the partial depolymerization of F-actin during muscle contraction. Taken together, our data show that DBN-1 organizes the muscle contractile apparatus maintaining the spatial relationship between actin-binding proteins such as a-actinin, tropomyosin and ADF/cofilin and possibly strengthening actin filaments by bundling.

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“…The forms differ in their filament severing and depolymerizing abilities and tissue locations. UNC-60A is required for proper early development and UNC-60B for muscle sarcomere structure (Ono and Benian, 1998;Ono et al, 1999Ono et al, , 2003Ono, 2003;Yamashiro et al, 2005). The C-terminal portion of UNC-60B is critical for its interactions with filamentous actin .…”

Section: Thin Filamentmentioning

confidence: 99%

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

Hooper

Hobbs

Thuma

2008

Progress in Neurobiology

128

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This is the second in a series of canonical reviews on invertebrate muscle. We cover here thin and thick filament structure, the molecular basis of force generation and its regulation, and two special properties of some invertebrate muscle, catch and asynchronous muscle. Invertebrate thin filaments resemble vertebrate thin filaments, although helix structure and tropomyosin arrangement show small differences. Invertebrate thick filaments, alternatively, are very different from vertebrate striated thick filaments and show great variation within invertebrates. Part of this diversity stems from variation in paramyosin content, which is greatly increased in very large diameter invertebrate thick filaments. Other of it arises from relatively small changes in filament backbone structure, which results in filaments with grossly similar myosin head placements (rotating crowns of heads every 14.5 nm) but large changes in detail (distances between heads in azimuthal registration varying from three to thousands of crowns). The lever arm basis of force generation is common to both vetebrates and invertebrates, and in some invertebrates this process is understood on the near atomic level. Invertebrate actomyosin is both thin (tropomyosin:troponin) and thick (primarily via direct Ca ++ binding to myosin) filament regulated, and most invertebrate muscles are dually regulated. These mechanisms are well understood on the molecular level, but the behavioral utility of dual regulation is less so. The phosphorylation state of the thick filament associated giant protein, twitchin, has been recently shown to be the molecular basis of catch. The molecular basis of the stretch activation underlying asynchronous muscle activity, however, remains unresolved.

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Two Caenorhabditis elegans Actin Depolymerizing Factor/Cofilin Proteins, Encoded by the unc-60 Gene, Differentially Regulate Actin Filament Dynamics

Cited by 91 publications

References 38 publications

The cofilin pathway in breast cancer invasion and metastasis

The cofilin pathway in breast cancer invasion and metastasis

Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

Invertebrate muscles: Thin and thick filament structure; molecular basis of contraction and its regulation, catch and asynchronous muscle

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