ZYX-1, the Unique Zyxin Protein of Caenorhabditis Elegans, is Involved in Dystrophin-dependent Muscle Degeneration
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Molecular Biology
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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.
Parmar B, Kieswetter A, Geens E, Vandewyer E, Ludwig C, Temmerman L PLoS Biol. 2023; 21(9):e3002300.
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Wei Z, Xia K, Zhou B, Zheng D, Guo W Biomedicines. 2023; 11(8).
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Slabodnick M, Tintori S, Prakash M, Zhang P, Higgins C, Chen A PLoS Genet. 2023; 19(3):e1010319.
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Serre J, Slabodnick M, Goldstein B, Hardin J PLoS Genet. 2023; 19(3):e1010507.
PMID: 36867663 PMC: 10016700. DOI: 10.1371/journal.pgen.1010507.
Lynch A, Zhu Y, Lucas B, Winkelman J, Bai K, Martin S Curr Biol. 2022; 32(23):5189-5199.e6.
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