title: The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance in Caenorhabditis elegans.
abstract: We describe the identification of zyxin as a regulator of synapse maintenance in mechanosensory neurons in C. elegans. zyx-1 mutants lacked PLM mechanosensory synapses as adult animals. However, most PLM synapses initially formed during development but were subsequently lost as the animals developed. Vertebrate zyxin regulates cytoskeletal responses to mechanical stress in culture. Our work provides in vivo evidence in support of such a role for zyxin. In particular, zyx-1 mutant synaptogenesis phenotypes were suppressed by disrupting locomotion of the mutant animals, suggesting that zyx-1 protects mechanosensory synapses from locomotion-induced forces. In cultured cells, zyxin is recruited to focal adhesions and stress fibers via C-terminal LIM domains and modulates cytoskeletal organization via the N-terminal domain. The synapse-stabilizing activity was mediated by a short isoform of ZYX-1 containing only the LIM domains. Consistent with this notion, PLM synaptogenesis was independent of α-actinin and ENA-VASP, both of which bind to the N-terminal domain of zyxin. Our results demonstrate that the LIM domain moiety of zyxin functions autonomously to mediate responses to mechanical stress and provide in vivo evidence for a role of zyxin in neuronal development.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110, USA Department of Neurology, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110, USA.
authors.forename: Anneliese M
authors.initials: AM
authors.lastname: Schaefer
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Dour
authors.affiliation: Department of Anatomy and Neurobiology, Washington University Medical School, 660 S Euclid Ave, St Louis, MO 63110, USA nonetm@pcg.wustl.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nonet
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009068:Movement; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry; D020033:Protein Isoforms / Q000502:physiology; D017434:Protein Structure, Tertiary; D013314:Stress, Mechanical; D013569:Synapses / Q000502:physiology*; D060589:Zyxin / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C532814:ZYX-1 protein, C elegans; D060589:Zyxin; D000185:Actinin
keywords: Axon retraction; Cytoskeleton; Stress fiber; Synaptogenesis