scholarly journals DYC-1, a Protein Functionally Linked to Dystrophin in Caenorhabditis elegans Is Associated with the Dense Body, Where It Interacts with the Muscle LIM Domain Protein ZYX-1

2008 ◽  
Vol 19 (3) ◽  
pp. 785-796 ◽  
Author(s):  
Claire Lecroisey ◽  
Edwige Martin ◽  
Marie-Christine Mariol ◽  
Laure Granger ◽  
Yannick Schwab ◽  
...  

In Caenorhabditis elegans, mutations of the dystrophin homologue, dys-1, produce a peculiar behavioral phenotype (hyperactivity and a tendency to hypercontract). In a sensitized genetic background, dys-1 mutations also lead to muscle necrosis. The dyc-1 gene was previously identified in a genetic screen because its mutation leads to the same phenotype as dys-1, suggesting that the two genes are functionally linked. Here, we report the detailed characterization of the dyc-1 gene. dyc-1 encodes two isoforms, which are expressed in neurons and muscles. Isoform-specific RNAi experiments show that the absence of the muscle isoform, and not that of the neuronal isoform, is responsible for the dyc-1 mutant phenotype. In the sarcomere, the DYC-1 protein is localized at the edges of the dense body, the nematode muscle adhesion structure where actin filaments are anchored and linked to the sarcolemma. In yeast two-hybrid assays, DYC-1 interacts with ZYX-1, the homologue of the vertebrate focal adhesion LIM domain protein zyxin. ZYX-1 localizes at dense bodies and M-lines as well as in the nucleus of C. elegans striated muscles. The DYC-1 protein possesses a highly conserved 19 amino acid sequence, which is involved in the interaction with ZYX-1 and which is sufficient for addressing DYC-1 to the dense body. Altogether our findings indicate that DYC-1 may be involved in dense body function and stability. This, taken together with the functional link between the C. elegans DYC-1 and DYS-1 proteins, furthermore suggests a requirement of dystrophin function at this structure. As the dense body shares functional similarity with both the vertebrate Z-disk and the costamere, we therefore postulate that disruption of muscle cell adhesion structures might be the primary event of muscle degeneration occurring in the absence of dystrophin, in C. elegans as well as vertebrates.

2013 ◽  
Vol 24 (8) ◽  
pp. 1232-1249 ◽  
Author(s):  
Claire Lecroisey ◽  
Nicolas Brouilly ◽  
Hiroshi Qadota ◽  
Marie-Christine Mariol ◽  
Nicolas C. Rochette ◽  
...  

In vertebrates, zyxin is a LIM-domain protein belonging to a family composed of seven members. We show that the nematode Caenorhabditis elegans has a unique zyxin-like protein, ZYX-1, which is the orthologue of the vertebrate zyxin subfamily composed of zyxin, migfilin, TRIP6, and LPP. The ZYX-1 protein is expressed in the striated body-wall muscles and localizes at dense bodies/Z-discs and M-lines, as well as in the nucleus. In yeast two-hybrid assays ZYX-1 interacts with several known dense body and M-line proteins, including DEB-1 (vinculin) and ATN-1 (α-actinin). ZYX-1 is mainly localized in the middle region of the dense body/Z-disk, overlapping the apical and basal regions containing, respectively, ATN-1 and DEB-1. The localization and dynamics of ZYX-1 at dense bodies depend on the presence of ATN-1. Fluorescence recovery after photobleaching experiments revealed a high mobility of the ZYX-1 protein within muscle cells, in particular at dense bodies and M-lines, indicating a peripheral and dynamic association of ZYX-1 at these muscle adhesion structures. A portion of the ZYX-1 protein shuttles from the cytoplasm into the nucleus, suggesting a role for ZYX-1 in signal transduction. We provide evidence that the zyx-1 gene encodes two different isoforms, ZYX-1a and ZYX-1b, which exhibit different roles in dystrophin-dependent muscle degeneration occurring in a C. elegans model of Duchenne muscular dystrophy.


2004 ◽  
Vol 165 (6) ◽  
pp. 857-867 ◽  
Author(s):  
Limor Broday ◽  
Irina Kolotuev ◽  
Christine Didier ◽  
Anindita Bhoumik ◽  
Benjamin Podbilewicz ◽  
...  

Here, we describe a new muscle LIM domain protein, UNC-95, and identify it as a novel target for the RING finger protein RNF-5 in the Caenorhabditis elegans body wall muscle. unc-95(su33) animals have disorganized muscle actin and myosin-containing filaments as a result of a failure to assemble normal muscle adhesion structures. UNC-95 is active downstream of PAT-3/β-integrin in the assembly pathways of the muscle dense body and M-line attachments, and upstream of DEB-1/vinculin in the dense body assembly pathway. The translational UNC-95::GFP fusion construct is expressed in dense bodies, M-lines, and muscle–muscle cell boundaries as well as in muscle cell bodies. UNC-95 is partially colocalized with RNF-5 in muscle dense bodies and its expression and localization are regulated by RNF-5. rnf-5(RNAi) or a RING domain deleted mutant, rnf-5(tm794), exhibit structural defects of the muscle attachment sites. Together, our data demonstrate that UNC-95 constitutes an essential component of muscle adhesion sites that is regulated by RNF-5.


Author(s):  
Masayo Kotaka ◽  
Sai-Ming Ngai ◽  
Merce Garcia-Barcelo ◽  
Stephen K.W. Tsui ◽  
Kwok-Pui Fung ◽  
...  

1998 ◽  
Vol 273 (47) ◽  
pp. 31547-31554 ◽  
Author(s):  
Marie-France Champliaud ◽  
Robert E. Burgeson ◽  
William Jin ◽  
Howard P. Baden ◽  
Pamela F. Olson

Gene ◽  
1998 ◽  
Vol 210 (2) ◽  
pp. 345-350 ◽  
Author(s):  
Kwok Keung Chan ◽  
Stephen Kwok Wing Tsui ◽  
Simon Ming Yuen Lee ◽  
Sharon Chui Wah Luk ◽  
Choong Chin Liew ◽  
...  

2013 ◽  
Vol 24 (5) ◽  
pp. 601-616 ◽  
Author(s):  
Adam Warner ◽  
Ge Xiong ◽  
Hiroshi Qadota ◽  
Teresa Rogalski ◽  
A. Wayne Vogl ◽  
...  

We identify cpna-1 (F31D5.3) as a novel essential muscle gene in the nematode Caenorhabditis elegans. Antibodies specific to copine domain protein atypical-1 (CPNA-1), as well as a yellow fluorescent protein translational fusion, are localized to integrin attachment sites (M-lines and dense bodies) in the body-wall muscle of C. elegans. CPNA-1 contains an N-terminal predicted transmembrane domain and a C-terminal copine domain and binds to the M-line/dense body protein PAT-6 (actopaxin) and the M-line proteins UNC-89 (obscurin), LIM-9 (FHL), SCPL-1 (SCP), and UNC-96. Proper CPNA-1 localization is dependent upon PAT-6 in embryonic and adult muscle. Nematodes lacking cpna-1 arrest elongation at the twofold stage of embryogenesis and display disruption of the myofilament lattice. The thick-filament component myosin heavy chain MYO-3 and the M-line component UNC-89 are initially localized properly in cpna-1–null embryos. However, in these embryos, when contraction begins, MYO-3 and UNC-89 become mislocalized into large foci and animals die. We propose that CPNA-1 acts as a linker between an integrin-associated protein, PAT-6, and membrane-distal components of integrin adhesion complexes in the muscle of C. elegans.


1997 ◽  
Vol 16 (4) ◽  
pp. 433-442 ◽  
Author(s):  
MICHELE GENINI ◽  
PETRA SCHWALBE ◽  
FLORENCE A. SCHOLL ◽  
ANDREW REMPPIS ◽  
MARIE-GENEVIÈVE MATTEI ◽  
...  

Gene ◽  
1999 ◽  
Vol 237 (1) ◽  
pp. 253-263 ◽  
Author(s):  
Simon Ming Yuen Lee ◽  
Hoi Yeung Li ◽  
Enders Kai On Ng ◽  
Simon Man Wai Or ◽  
Kwok Keung Chan ◽  
...  

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