The Cytoskeletal Regulator Zyxin is Required for Viability in Drosophila melanogaster

Abstract

The zyxin family of proteins function as cytoskeletal regulators in adhesion, actin assembly, and cell motility. Though fibroblasts derived from zyxin-null mice show striking defects in motility and response to mechanical stimuli, the mice are viable and fertile. In Drosophila melanogaster, the family is represented by a single homologue, Zyx102. To study the role of zyxin during development, we generated a zyx102 RNA-interference transgenic line that allows for the conditional knockdown of Zyx102. When UAST-zyx102-dsRNAi expression is driven broadly by Actin5C-GAL4, loss of Zyx102 results in lethality during the pharate adult stage, a narrow developmental window during which the fly must molt, resorb molting fluid, fill adult trachea with air and execute a behavioral program to eclose. Zyx102 knockdown animals attempt to emerge, but their adult trachea do not fill with air. If dissected from the pupal case, knockdown individuals appear morphologically normal, but remain inviable.

Zyxin Links Fat Signaling to the Hippo Pathway

“…The most promising candidates were then taken through four additional tests, involving confirmation of effects on additional downstream target genes, characterization of phenotypes when expressed under additional Gal4 drivers, confirmation of phenotypes with additional, independent UAS-RNAi lines, and characterization of genetic interactions with known pathway components. Based on these experiments, a single gene, Zyx102 ( Zyx ) [11] , [12] , which is located at 102F7 near the tip of the fourth chromosome, was identified as a novel component of the Fat-Hippo signaling pathway.…”

“…Zyx is a Drosophila homologue of the vertebrate Zyxin, Lipoma preferred partner (LPP), and Thyroid-receptor interacting protein 6 (TRIP6) proteins [11] , [12] . These proteins have three conserved LIM domains at their C-terminus, and they have been implicated in both cytoskeletal and transcriptional regulation [13] – [15] .…”

Remodeling Tissue Interfaces and the Thermodynamics of Zipping during Dorsal Closure in Drosophila

“…References (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) appear in the Supporting Material.…”

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance in Caenorhabditis elegans

“…Various family members have been implicated in diverse processes including microRNA-mediated gene silencing (James et al, 2010), responses to hypoxia (Foxler et al, 2012), hippo signaling (Das Thakur et al, 2010), PIP2 signaling (Kisseleva et al, 2005) and stress fiber maintenance (Smith et al, 2010;Hoffman et al, 2012). Molecular genetic analysis in mouse suggests that vertebrate zyxin family members assume functionally redundant cellular roles, since mouse knockouts of LPP and zyxin exhibit few overt phenotypic abnormalities (Hoffman et al, 2003;Vervenne et al, 2009), whereas Drosophila mutants are inviable (Das Thakur et al, 2010;Renfranz et al, 2010).…”