Smurf Downregulates Echinoid in the Amnioserosa To Regulate Drosophila Dorsal Closure

Abstract

dorsal closure is a morphogenetic movement that involves flanking epidermal cells, assembling actomyosin cables, and migrating dorsally over the underlying amnioserosa to seal at the dorsal midline. Echinoid (Ed)-a cell adhesion molecule of adherens junctions (AJs)-participates in several developmental processes. The disappearance of Ed from the amnioserosa is required to define the epidermal leading edge for actomyosin cable assembly and coordinated cell migration. However, the mechanism by which Ed is cleared from amnioserosa is unknown. Here, we show that Ed is cleared in amnioserosa by both transcriptional and post-translational mechanisms. First, mRNA transcription was repressed in amnioserosa prior to the onset of dorsal closure. Second, the ubiquitin ligase Smurf downregulated pretranslated Ed by binding to the PPXY motif of Ed. During dorsal closure, Smurf colocalized with Ed at AJs, and Smurf overexpression prematurely degraded Ed in the amnioserosa. Conversely, Ed persisted in the amnioserosa of mutant embryos, which, in turn, affected actomyosin cable formation. Together, our results demonstrate that transcriptional repression of followed by Smurf-mediated downregulation of pretranslated Ed in amnioserosa regulates the establishment of a taut leading edge during dorsal closure.

Commissureless acts as a substrate adapter in a conserved Nedd4 E3 ubiquitin ligase pathway to promote axon growth across the midline

“…However, these approaches were not successful, presumably due to the necessity of Nedd4-family ligases in oogenesis (Xia et al, 2010) as well as early patterning events and cell fate decisions that occur before axon guidance begins. ((Bakkers et al, 2005; Lin et al, 2017; Lohraseb et al, 2022; Persaud et al, 2011; Podos et al, 2001; Zhang et al, 2014)).…”

Single Nucleotide Polymorphisms of Ubiquitin-Related Genes were Associated with Allograft Fibrosis of Renal Transplant Fibrosis

“…However, results from a previous related study by authors of this manuscript found that having a 1 or 2 copies of the risk allele appeared to significantly increase the ubiquitin-related gene Smurf2 transcript level in biopsied tissues from the allograft treatment group [17]. Smurf2 mRNA expression increased with the expression of TGF-β1 in the early stages of renal fibrosis and development and it is possible that various methods to induce and enhance Smurf2 expression could be used to some extent in order to slow or prevent the progression of allograft fibrosis [18]. Other ubiquitin-related genes were insignificant in our related analyses which may have resulted because the signal pathways associated with them are yet to be clearly identified.…”

Orchestrating morphogenesis: building the body plan by cell shape changes and movements

“…Another key cue is provided by the nectin relative Echinoid. As in other tissues, an actin cable assembles at the border between cells expressing Echinoid (in this case the epidermis) and those in which Echinoid is absent (in this case the amnioserosa) (Laplante and Nilson, 2011;Lin et al, 2017Lin et al, , 2007.…”