Biology subjects

Gouignard, N.

Publications and source records attributed to Gouignard, N..

3 recordsLinked to original sources

bioRxiv2026

An Evolutionarily Conserved Ypk1/SGK1 Kinase Pathway Regulates the Unfolded Protein Response by Modulating the Ire1 Protein Abundance

The unfolded protein response (UPR) is a cellular mechanism that maintains protein homeostasis (proteostasis) under conditions of endoplasmic reticulum (ER) stress. The dual kinase/RNase Ire1 is a conserved regulator of the UPR, mediating the unconventional cytosolic splicing of HAC1 mRNA in yeast and XBP1 mRNA in human cells. The resulting spliced HAC1/XBP1 transcript encodes a transcription factor that induces the expression of protein-folding chaperones and stress-responsive genes, thereby restoring proteostasis. In our previous work, we showed that the MAP kinase Slt2 (homolog of human ERKs) contributes to UPR signaling by promoting IRE1 expression through the transcription factor Rlm1 (homolog of human MEF2C). Here, we demonstrate that Hac1 expression is reduced in yeast strains deficient in essential protein kinase Cdc28, Pkc1, Rio2, Tor2, Pkh1, or Ypk1, suggesting that these kinases also serve as UPR regulators. We focused on the kinase Ypk1, the yeast ortholog of human SGK1 (serum/glucocorticoid-regulated kinase 1). We provide genetic and biochemical evidence that Ypk1/SGK1 acts upstream of the Pkc1/PKC{delta} signaling pathway and is required for maintaining IRE1 protein abundance in both yeast and human cells. Collectively, our results identify an evolutionarily conserved Ypk1/SGK1 signaling pathway that regulates the HAC1 and XBP1 mRNA splicing by modulating the Ire1 protein abundance.

genetics↗

bioRxiv2019

Dynamic expression of MMP28 during cranial morphogenesis

Matrix metalloproteinases (MMP) are a large family of proteases comprising 24 members in vertebrates. They are well known for their extracellular matrix remodelling activity. MMP28 is the last member of the family to be discovered. It is a secreted MMP involved in wound healing, immune system maturation, cell survival and migration. MMP28 is also expressed during embryogenesis in human and mouse. Here we describe the detailed expression profile of MMP28 in Xenopus laevis embryos. We show that MMP28 is expressed maternally and accumulates at neurula and tailbud stages specifically in the cranial placode territories adjacent to migrating neural crest cells. As a secreted MMP, MMP28 may be required in normal neural crest-placode interactions.

developmental biology↗

bioRxiv2018

In vivo topology converts competition for cell-matrix adhesion into directional migration

When migrating in vivo, cells are exposed to numerous, and somewhat conflicting, signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Our results indicate that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.

developmental biology↗